AU2018347349A1 - Process for preparing spiro derivatives - Google Patents
Process for preparing spiro derivatives Download PDFInfo
- Publication number
- AU2018347349A1 AU2018347349A1 AU2018347349A AU2018347349A AU2018347349A1 AU 2018347349 A1 AU2018347349 A1 AU 2018347349A1 AU 2018347349 A AU2018347349 A AU 2018347349A AU 2018347349 A AU2018347349 A AU 2018347349A AU 2018347349 A1 AU2018347349 A1 AU 2018347349A1
- Authority
- AU
- Australia
- Prior art keywords
- compound
- preparing
- followed
- methyl
- solution
- 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.)
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- 125000003003 spiro group Chemical group 0.000 title abstract description 5
- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 52
- 150000001875 compounds Chemical class 0.000 claims description 155
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 24
- PMWWAUBENRRILR-ZDUSSCGKSA-N tert-butyl n-[(3s)-1-methyl-2-oxo-3-prop-2-ynylpyrrolidin-3-yl]carbamate Chemical compound CN1CC[C@](CC#C)(NC(=O)OC(C)(C)C)C1=O PMWWAUBENRRILR-ZDUSSCGKSA-N 0.000 claims description 19
- BOCIWLBENJQNBZ-VIFPVBQESA-N (3S)-1-methyl-2-oxo-3-prop-2-ynylpyrrolidine-3-carboxylic acid Chemical compound CN1C([C@](CC1)(C(=O)O)CC#C)=O BOCIWLBENJQNBZ-VIFPVBQESA-N 0.000 claims description 10
- UXDUCKXHQNXZNH-CRKQZGGQSA-N [(1S)-2-hydroxy-1-phenylethyl]azanium (3S)-1-methyl-2-oxo-3-prop-2-ynylpyrrolidine-3-carboxylate Chemical compound N[C@@H](C1=CC=CC=C1)CO.CN1C([C@](CC1)(C(=O)O)CC#C)=O UXDUCKXHQNXZNH-CRKQZGGQSA-N 0.000 claims description 10
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 10
- GCZUIPVRHLYYOG-UHFFFAOYSA-N 7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one Chemical compound O=C1N(C)CCC11NC(C=2N=C(C=C(C)N=2)C=2C=CC(=CC=2)C(F)(F)F)CC1 GCZUIPVRHLYYOG-UHFFFAOYSA-N 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 100
- 239000000243 solution Substances 0.000 description 63
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- 239000007787 solid Substances 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 239000012065 filter cake Substances 0.000 description 13
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- BOCIWLBENJQNBZ-UHFFFAOYSA-N 1-methyl-2-oxo-3-prop-2-ynylpyrrolidine-3-carboxylic acid Chemical compound CN1C(C(CC1)(C(=O)O)CC#C)=O BOCIWLBENJQNBZ-UHFFFAOYSA-N 0.000 description 7
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000004744 fabric Substances 0.000 description 7
- 229910000160 potassium phosphate Inorganic materials 0.000 description 7
- 235000011009 potassium phosphates Nutrition 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- SJNRTFLAHLDZAW-UHFFFAOYSA-N ethyl 1-methyl-2-oxo-3-prop-2-ynylpyrrolidine-3-carboxylate Chemical compound CN1C(C(CC1)(C(=O)OCC)CC#C)=O SJNRTFLAHLDZAW-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 239000012455 biphasic mixture Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 5
- 229940011051 isopropyl acetate Drugs 0.000 description 5
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- LHTKZFMYGHEHTF-UHFFFAOYSA-N tert-butyl 1-methyl-2-oxo-3-prop-2-ynylpyrrolidine-3-carboxylate Chemical compound CN1C(C(CC1)(C(=O)OC(C)(C)C)CC#C)=O LHTKZFMYGHEHTF-UHFFFAOYSA-N 0.000 description 5
- SFWAHUCHFDWXTL-UHFFFAOYSA-N tert-butyl 1-methyl-2-oxopyrrolidine-3-carboxylate Chemical compound CN1CCC(C(=O)OC(C)(C)C)C1=O SFWAHUCHFDWXTL-UHFFFAOYSA-N 0.000 description 5
- CIBIQCRUDYBRJO-IBGZPJMESA-N (5s)-7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one Chemical compound O=C1N(C)CC[C@]11N=C(C=2N=C(C=C(C)N=2)C=2C=CC(=CC=2)C(F)(F)F)CC1 CIBIQCRUDYBRJO-IBGZPJMESA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 239000004677 Nylon Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000002051 biphasic effect Effects 0.000 description 4
- 229920001778 nylon Polymers 0.000 description 4
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- WUULVIOWIRBAFW-WSCVZUBPSA-N (2r,5s)-7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;sulfuric acid Chemical compound OS(O)(=O)=O.O=C1N(C)CC[C@]11N[C@@H](C=2N=C(C=C(C)N=2)C=2C=CC(=CC=2)C(F)(F)F)CC1 WUULVIOWIRBAFW-WSCVZUBPSA-N 0.000 description 3
- IWGKDUCONLPNEM-FYZYNONXSA-N (3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one 2-hydroxybenzoic acid Chemical compound OC1=C(C(=O)O)C=CC=C1.N[C@@]1(C(N(CC1)C)=O)CC#CC1=NC(=CC(=N1)C)C1=CC=C(C=C1)C(F)(F)F IWGKDUCONLPNEM-FYZYNONXSA-N 0.000 description 3
- GZUUTWXPONLFKU-UHFFFAOYSA-N 2-chloro-4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidine Chemical compound ClC1=NC(C)=CC(C=2C=CC(=CC=2)C(F)(F)F)=N1 GZUUTWXPONLFKU-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical group [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 229940043279 diisopropylamine Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- -1 carboxylic acid compound Chemical class 0.000 description 2
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 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 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- PWYKAPTWUKNYOC-WSCVZUBPSA-N (2r,5s)-7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;hydrochloride Chemical compound Cl.O=C1N(C)CC[C@]11N[C@@H](C=2N=C(C=C(C)N=2)C=2C=CC(=CC=2)C(F)(F)F)CC1 PWYKAPTWUKNYOC-WSCVZUBPSA-N 0.000 description 1
- HRRJQMJJEMZBCF-HOOCCGKBSA-N (2r,5s)-7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one;sulfuric acid;hydrate Chemical compound O.OS(O)(=O)=O.O=C1N(C)CC[C@]11N[C@@H](C=2N=C(C=C(C)N=2)C=2C=CC(=CC=2)C(F)(F)F)CC1 HRRJQMJJEMZBCF-HOOCCGKBSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- BTLKROSJMNFSQZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(Cl)=N1 BTLKROSJMNFSQZ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- SLNQYJKNUXSPIC-HOOCCGKBSA-N C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(CC(O)(C(=O)O)CC(=O)O)(=O)O.CN1C([C@]2(CC[C@@H](N2)C2=NC(=CC(=N2)C)C2=CC=C(C=C2)C(F)(F)F)CC1)=O Chemical compound C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(CC(O)(C(=O)O)CC(=O)O)(=O)O.CN1C([C@]2(CC[C@@H](N2)C2=NC(=CC(=N2)C)C2=CC=C(C=C2)C(F)(F)F)CC1)=O SLNQYJKNUXSPIC-HOOCCGKBSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- PUMOKLJIGPVXND-HOOCCGKBSA-N S(C)(=O)(=O)O.CS(=O)(=O)O.CN1C([C@]2(CC[C@@H](N2)C2=NC(=CC(=N2)C)C2=CC=C(C=C2)C(F)(F)F)CC1)=O Chemical compound S(C)(=O)(=O)O.CS(=O)(=O)O.CN1C([C@]2(CC[C@@H](N2)C2=NC(=CC(=N2)C)C2=CC=C(C=C2)C(F)(F)F)CC1)=O PUMOKLJIGPVXND-HOOCCGKBSA-N 0.000 description 1
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 1
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 1
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010943 off-gassing Methods 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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 to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
- C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
- C07C65/05—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring o-Hydroxy carboxylic acids
- C07C65/10—Salicylic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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 to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Measuring Volume Flow (AREA)
- Exhaust Gas After Treatment (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762570269P | 2017-10-10 | 2017-10-10 | |
| US62/570,269 | 2017-10-10 | ||
| PCT/US2018/055227 WO2019075073A2 (en) | 2017-10-10 | 2018-10-10 | PROCESS FOR THE PREPARATION OF SPIRO DERIVATIVES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018347349A1 true AU2018347349A1 (en) | 2020-04-23 |
Family
ID=66100090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018347349A Withdrawn AU2018347349A1 (en) | 2017-10-10 | 2018-10-10 | Process for preparing spiro derivatives |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US11149039B2 (OSRAM) |
| EP (1) | EP3694510A4 (OSRAM) |
| JP (1) | JP2020536898A (OSRAM) |
| KR (1) | KR20200068678A (OSRAM) |
| CN (1) | CN111526874A (OSRAM) |
| AU (1) | AU2018347349A1 (OSRAM) |
| CA (1) | CA3077088A1 (OSRAM) |
| IL (1) | IL273695A (OSRAM) |
| MA (1) | MA50371A (OSRAM) |
| MX (2) | MX2020003821A (OSRAM) |
| SG (1) | SG11202002707VA (OSRAM) |
| WO (1) | WO2019075073A2 (OSRAM) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2018347349A1 (en) | 2017-10-10 | 2020-04-23 | Biogen Inc. | Process for preparing spiro derivatives |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US814396A (en) | 1905-05-22 | 1906-03-06 | Joseph R Russell | Burner for liquid fuel. |
| KR0178475B1 (ko) | 1995-09-14 | 1999-03-20 | 윤덕용 | 신규한 n-비닐락탐 유도체 및 그의 중합체 |
| EP1519939B9 (en) | 2002-07-05 | 2011-04-06 | Targacept, Inc. | N-aryl diazaspirocyclic compounds and methods of preparation and use thereof |
| US7501528B2 (en) | 2005-03-15 | 2009-03-10 | Hoffmann-La Roche Inc. | Method for preparing enantiomerically pure 4-pyrrolidino phenylbenzyl ether derivatives |
| US8143306B2 (en) | 2005-10-10 | 2012-03-27 | Convergence Pharmaceuticals Limited | Methods of treating bipolar disorders |
| TW200728258A (en) | 2005-10-10 | 2007-08-01 | Glaxo Group Ltd | Novel compounds |
| DE602006015215D1 (de) | 2005-10-10 | 2010-08-12 | Glaxo Group Ltd | Prolinamidderivate als natriumkanalmodulatoren |
| GB0520578D0 (en) | 2005-10-10 | 2005-11-16 | Glaxo Group Ltd | Novel compounds |
| TW200730494A (en) | 2005-10-10 | 2007-08-16 | Glaxo Group Ltd | Novel compounds |
| AR063278A1 (es) | 2006-10-12 | 2009-01-14 | Xenon Pharmaceuticals Inc | Compuestos de espiro-oxindol, una composicion farmaceutica que los comprende y su uso para el tratamiento de enfermedades o condiciones mediadas por los canales de sodio. |
| AU2007307635A1 (en) | 2006-10-12 | 2008-04-17 | Xenon Pharmaceuticals Inc. | Tricyclic spiro-oxindole derivatives and their uses as therapeutic agents |
| WO2008090114A1 (en) | 2007-01-24 | 2008-07-31 | Glaxo Group Limited | Pharmaceutical compositions comprising 2-methoxy-5- (5-trifluoromethyl-tetrazol-i-yl-benzyl) - (2s-phenyl-piperidin-3s-yl-) |
| GB0701366D0 (en) | 2007-01-24 | 2007-03-07 | Glaxo Group Ltd | Novel pharmaceutical compositions |
| GB0701365D0 (en) | 2007-01-24 | 2007-03-07 | Glaxo Group Ltd | Novel pharmaceutical compositions |
| GB0706630D0 (en) | 2007-04-04 | 2007-05-16 | Glaxo Group Ltd | Novel compounds |
| AR077252A1 (es) | 2009-06-29 | 2011-08-10 | Xenon Pharmaceuticals Inc | Enantiomeros de compuestos de espirooxindol y sus usos como agentes terapeuticos |
| TWI466885B (zh) * | 2009-07-31 | 2015-01-01 | Japan Tobacco Inc | 含氮螺環化合物及其醫藥用途 |
| HRP20150491T1 (hr) | 2009-09-14 | 2015-08-14 | Convergence Pharmaceuticals Limited | PROCES PRIPREME DERIVATA α-KARBOKSAMIDA |
| US8618303B2 (en) | 2011-01-07 | 2013-12-31 | Hoffmann-La Roche Inc. | Pyrrolidine derivatives |
| BR112013026116A2 (pt) * | 2011-04-26 | 2016-12-27 | Hoffmann La Roche | derivados etinílicos como moduladores alostéricos positivos de mglur5 |
| GB201122113D0 (en) * | 2011-12-22 | 2012-02-01 | Convergence Pharmaceuticals | Novel compounds |
| GB201209015D0 (en) | 2012-05-22 | 2012-07-04 | Convergence Pharmaceuticals | Novel compounds |
| GB201209670D0 (en) | 2012-05-31 | 2012-07-18 | Convergence Pharmaceuticals | Novel compounds |
| KR102485537B1 (ko) | 2014-08-04 | 2023-01-05 | 메르크 파텐트 게엠베하 | Metap-2 저해제로서의 피롤리디논 유도체 |
| MA50669A (fr) | 2017-09-28 | 2020-08-05 | Biogen Inc | Nouveaux sels |
| AU2018347349A1 (en) | 2017-10-10 | 2020-04-23 | Biogen Inc. | Process for preparing spiro derivatives |
-
2018
- 2018-10-10 AU AU2018347349A patent/AU2018347349A1/en not_active Withdrawn
- 2018-10-10 CN CN201880066263.9A patent/CN111526874A/zh not_active Withdrawn
- 2018-10-10 JP JP2020520223A patent/JP2020536898A/ja not_active Withdrawn
- 2018-10-10 US US16/754,044 patent/US11149039B2/en not_active Expired - Fee Related
- 2018-10-10 EP EP18866634.1A patent/EP3694510A4/en not_active Withdrawn
- 2018-10-10 MX MX2020003821A patent/MX2020003821A/es unknown
- 2018-10-10 WO PCT/US2018/055227 patent/WO2019075073A2/en not_active Ceased
- 2018-10-10 CA CA3077088A patent/CA3077088A1/en not_active Withdrawn
- 2018-10-10 SG SG11202002707VA patent/SG11202002707VA/en unknown
- 2018-10-10 KR KR1020207011962A patent/KR20200068678A/ko not_active Withdrawn
- 2018-10-10 MA MA050371A patent/MA50371A/fr unknown
-
2020
- 2020-03-30 IL IL273695A patent/IL273695A/en unknown
- 2020-07-13 MX MX2022013928A patent/MX2022013928A/es unknown
-
2021
- 2021-10-15 US US17/502,653 patent/US20220033408A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP3694510A4 (en) | 2021-06-30 |
| MA50371A (fr) | 2021-03-31 |
| IL273695A (en) | 2020-05-31 |
| JP2020536898A (ja) | 2020-12-17 |
| WO2019075073A3 (en) | 2020-04-02 |
| US20200325144A1 (en) | 2020-10-15 |
| KR20200068678A (ko) | 2020-06-15 |
| MX2020003821A (es) | 2023-01-12 |
| CA3077088A1 (en) | 2019-04-18 |
| SG11202002707VA (en) | 2020-04-29 |
| CN111526874A (zh) | 2020-08-11 |
| US11149039B2 (en) | 2021-10-19 |
| WO2019075073A2 (en) | 2019-04-18 |
| US20220033408A1 (en) | 2022-02-03 |
| MX2022013928A (es) | 2022-11-30 |
| EP3694510A2 (en) | 2020-08-19 |
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| Date | Code | Title | Description |
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| MK12 | Application lapsed section 141(1)/reg 8.3(2) - applicant filed a written notice of withdrawal |