CN101812026A - 一种硼替佐米的合成方法 - Google Patents
一种硼替佐米的合成方法 Download PDFInfo
- Publication number
- CN101812026A CN101812026A CN 201010145281 CN201010145281A CN101812026A CN 101812026 A CN101812026 A CN 101812026A CN 201010145281 CN201010145281 CN 201010145281 CN 201010145281 A CN201010145281 A CN 201010145281A CN 101812026 A CN101812026 A CN 101812026A
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- China
- Prior art keywords
- boric acid
- acid ester
- pinacol
- phenylalanine
- methyl
- 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.)
- Granted
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- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 title claims abstract description 35
- 229960001467 bortezomib Drugs 0.000 title abstract description 14
- 238000000034 method Methods 0.000 title abstract description 7
- 230000002194 synthesizing effect Effects 0.000 title abstract 3
- 239000004327 boric acid Substances 0.000 claims abstract description 68
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- YGHRJJRRZDOVPD-UHFFFAOYSA-N 3-methylbutanal Chemical compound CC(C)CC=O YGHRJJRRZDOVPD-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000009833 condensation Methods 0.000 claims abstract description 20
- 230000005494 condensation Effects 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 16
- -1 boric acid ester Chemical class 0.000 claims abstract description 13
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 claims abstract description 12
- JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 claims abstract description 10
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims abstract description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims abstract description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 24
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 22
- IVDFJHOHABJVEH-UHFFFAOYSA-N HOCMe2CMe2OH Natural products CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- 229940099039 velcade Drugs 0.000 claims description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- 238000010189 synthetic method Methods 0.000 claims description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 11
- 229960005190 phenylalanine Drugs 0.000 claims description 11
- 239000003054 catalyst Substances 0.000 claims description 10
- UZSHZSKRMRELMP-GFCCVEGCSA-N 3-methyl-N-[(1R)-1-phenylethyl]butan-1-imine Chemical compound CC(C)CC=N[C@H](C)C1=CC=CC=C1 UZSHZSKRMRELMP-GFCCVEGCSA-N 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 7
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 7
- JCVXOCUOIMRVHT-UHFFFAOYSA-N B(O)(O)O.CC(C)C Chemical compound B(O)(O)O.CC(C)C JCVXOCUOIMRVHT-UHFFFAOYSA-N 0.000 claims description 7
- 238000005885 boration reaction Methods 0.000 claims description 7
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
- 239000012964 benzotriazole Substances 0.000 claims description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000002524 organometallic group Chemical group 0.000 claims description 4
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 claims description 4
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- YHWCPXVTRSHPNY-UHFFFAOYSA-N butan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCC[O-].CCCC[O-].CCCC[O-].CCCC[O-] YHWCPXVTRSHPNY-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 claims description 3
- 229940045803 cuprous chloride Drugs 0.000 claims description 3
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims description 3
- UZSHZSKRMRELMP-UHFFFAOYSA-N 3-methyl-N-(1-phenylethyl)butan-1-imine Chemical compound CC(C)CC=NC(C)C1=CC=CC=C1 UZSHZSKRMRELMP-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 2
- 229910052792 caesium Inorganic materials 0.000 claims description 2
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 2
- QVLQKWQNKGVECJ-UHFFFAOYSA-N copper;propanoic acid Chemical compound [Cu].CCC(O)=O QVLQKWQNKGVECJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 239000010936 titanium Substances 0.000 claims description 2
- 229910052719 titanium Inorganic materials 0.000 claims description 2
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 5
- 238000010511 deprotection reaction Methods 0.000 abstract description 3
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 abstract 1
- 230000020477 pH reduction Effects 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 17
- 239000000047 product Substances 0.000 description 14
- 239000012043 crude product Substances 0.000 description 12
- 238000001035 drying Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 208000034578 Multiple myelomas Diseases 0.000 description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000012317 TBTU Substances 0.000 description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
- 229910052796 boron Inorganic materials 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000004575 stone Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 238000006713 insertion reaction Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- WGLLSSPDPJPLOR-UHFFFAOYSA-N tetramethylethylene Natural products CC(C)=C(C)C WGLLSSPDPJPLOR-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZZPNDIHOQDQVNU-UHFFFAOYSA-N 2-hydroxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(O)OC1(C)C ZZPNDIHOQDQVNU-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003368 amide group Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000012550 audit Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
Abstract
Description
Claims (10)
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102659919A (zh) * | 2012-05-23 | 2012-09-12 | 合肥工业大学 | 一种硼替佐米的合成方法 |
CN102898501A (zh) * | 2012-09-27 | 2013-01-30 | 朱锦桃 | 以(-)-雪松二醇为手性辅助剂制备硼替佐米的方法 |
CN103044467A (zh) * | 2011-10-14 | 2013-04-17 | 重庆安格龙翔医药科技有限公司 | 一种制备用于合成硼替佐米的中间体的方法 |
CN103059054A (zh) * | 2013-01-08 | 2013-04-24 | 杭州平和安康医药科技有限公司 | 硼替佐米合成方法 |
CN103304629A (zh) * | 2013-06-26 | 2013-09-18 | 江苏奥赛康药业股份有限公司 | 一种高光学纯度硼替佐米的制备方法及其中间体 |
CN103554219A (zh) * | 2013-10-01 | 2014-02-05 | 昆明贵研药业有限公司 | 一种制备硼替佐米的方法 |
CN104211758A (zh) * | 2013-05-29 | 2014-12-17 | 深圳翰宇药业股份有限公司 | 一种硼替佐米的制备方法 |
CN104387409A (zh) * | 2012-05-11 | 2015-03-04 | 人福医药集团股份公司 | 催化剂及其应用 |
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CN1305475C (zh) * | 1994-10-28 | 2007-03-21 | 千年药物公司 | 硼酸酯和硼酸化合物,其合成和应用 |
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CN1960996A (zh) * | 2004-03-30 | 2007-05-09 | 千禧药品公司 | 硼的酯和酸化合物的合成 |
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Cited By (11)
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CN103044467A (zh) * | 2011-10-14 | 2013-04-17 | 重庆安格龙翔医药科技有限公司 | 一种制备用于合成硼替佐米的中间体的方法 |
CN103044467B (zh) * | 2011-10-14 | 2015-03-04 | 重庆安格龙翔医药科技有限公司 | 一种制备用于合成硼替佐米的中间体的方法 |
CN104387409A (zh) * | 2012-05-11 | 2015-03-04 | 人福医药集团股份公司 | 催化剂及其应用 |
CN104387409B (zh) * | 2012-05-11 | 2017-09-29 | 人福医药集团股份公司 | 催化剂及其应用 |
CN102659919A (zh) * | 2012-05-23 | 2012-09-12 | 合肥工业大学 | 一种硼替佐米的合成方法 |
CN102659919B (zh) * | 2012-05-23 | 2016-03-30 | 合肥工业大学 | 一种硼替佐米的合成方法 |
CN102898501A (zh) * | 2012-09-27 | 2013-01-30 | 朱锦桃 | 以(-)-雪松二醇为手性辅助剂制备硼替佐米的方法 |
CN103059054A (zh) * | 2013-01-08 | 2013-04-24 | 杭州平和安康医药科技有限公司 | 硼替佐米合成方法 |
CN104211758A (zh) * | 2013-05-29 | 2014-12-17 | 深圳翰宇药业股份有限公司 | 一种硼替佐米的制备方法 |
CN103304629A (zh) * | 2013-06-26 | 2013-09-18 | 江苏奥赛康药业股份有限公司 | 一种高光学纯度硼替佐米的制备方法及其中间体 |
CN103554219A (zh) * | 2013-10-01 | 2014-02-05 | 昆明贵研药业有限公司 | 一种制备硼替佐米的方法 |
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