ZA200703603B - Macrolones - amino substituted quinolones - Google Patents

Info

Publication number

ZA200703603B

ZA200703603B ZA200703603A ZA200703603A ZA200703603B ZA 200703603 B ZA200703603 B ZA 200703603B ZA 200703603 A ZA200703603 A ZA 200703603A ZA 200703603 A ZA200703603 A ZA 200703603A ZA 200703603 B ZA200703603 B ZA 200703603B

Authority

ZA

South Africa

Prior art keywords

dihydro

oxo

carboxy

dimethylamino

erythromycin

Prior art date

2004-11-11

Links

• Espacenet
• Global Dossier
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• 229920004011 Macrolon® Polymers 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 413
• 229960003276 erythromycin Drugs 0.000 claims description 171
• 229960002626 clarithromycin Drugs 0.000 claims description 107
• ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Natural products O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 86
• 238000006243 chemical reaction Methods 0.000 claims description 78
• -1 -OR'TM Inorganic materials 0.000 claims description 73
• 229910052739 hydrogen Inorganic materials 0.000 claims description 71
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 71
• 239000001257 hydrogen Substances 0.000 claims description 70
• 238000000034 method Methods 0.000 claims description 65
• 125000006308 propyl amino group Chemical group 0.000 claims description 52
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 48
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 45
• 125000000623 heterocyclic group Chemical group 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 39
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 37
• 229910052757 nitrogen Inorganic materials 0.000 claims description 32
• 229960004099 azithromycin Drugs 0.000 claims description 29
• 125000000217 alkyl group Chemical group 0.000 claims description 28
• 125000004122 cyclic group Chemical group 0.000 claims description 27
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
• 150000002431 hydrogen Chemical class 0.000 claims description 21
• 229930006677 Erythromycin A Natural products 0.000 claims description 20
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 19
• 238000002360 preparation method Methods 0.000 claims description 19
• 238000011282 treatment Methods 0.000 claims description 19
• 241000282414 Homo sapiens Species 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 18
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 18
• 125000006239 protecting group Chemical group 0.000 claims description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 125000003118 aryl group Chemical group 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
• 230000008569 process Effects 0.000 claims description 15
• 125000004429 atom Chemical group 0.000 claims description 14
• 229910052760 oxygen Inorganic materials 0.000 claims description 14
• 239000001301 oxygen Substances 0.000 claims description 14
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims description 12
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 239000003085 diluting agent Substances 0.000 claims description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims description 11
• 125000005842 heteroatom Chemical group 0.000 claims description 11
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
• 239000003054 catalyst Substances 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• 239000011593 sulfur Chemical group 0.000 claims description 10
• 150000002923 oximes Chemical class 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical group NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 claims description 6
• 241001465754 Metazoa Species 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 5
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 208000015181 infectious disease Diseases 0.000 claims description 5
• 230000000813 microbial effect Effects 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 238000011321 prophylaxis Methods 0.000 claims description 5
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 230000000699 topical effect Effects 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• 125000002619 bicyclic group Chemical group 0.000 claims description 4
• 239000011737 fluorine Substances 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 230000009885 systemic effect Effects 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 239000003638 chemical reducing agent Substances 0.000 claims description 2
• TYQXKHPOXXXCTP-CSLYCKPJSA-N erythromycin A 2'-propanoate Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)OC(=O)CC)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 TYQXKHPOXXXCTP-CSLYCKPJSA-N 0.000 claims description 2
• 229950001028 erythromycin propionate Drugs 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 1
• 101150065749 Churc1 gene Proteins 0.000 claims 1
• 102100038239 Protein Churchill Human genes 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 657
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 426
• 239000000543 intermediate Substances 0.000 description 244
• 239000000243 solution Substances 0.000 description 204
• 239000000203 mixture Substances 0.000 description 197
• 230000002829 reductive effect Effects 0.000 description 191
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 190
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 173
• 239000007787 solid Substances 0.000 description 162
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 146
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 141
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 127
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 124
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 118
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 116
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 99
• 239000000741 silica gel Substances 0.000 description 95
• 229910002027 silica gel Inorganic materials 0.000 description 95
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 78
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 68
• 235000019439 ethyl acetate Nutrition 0.000 description 64
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
• 229910021529 ammonia Inorganic materials 0.000 description 54
• 238000004587 chromatography analysis Methods 0.000 description 52
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 51
• 239000002904 solvent Substances 0.000 description 51
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• 238000003756 stirring Methods 0.000 description 45
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 44
• 239000006260 foam Substances 0.000 description 41
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 39
• 229910052786 argon Inorganic materials 0.000 description 39
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
• 239000003480 eluent Substances 0.000 description 35
• 235000019253 formic acid Nutrition 0.000 description 34
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 33
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
• 239000000725 suspension Substances 0.000 description 28
• 239000012267 brine Substances 0.000 description 27
• 239000012044 organic layer Substances 0.000 description 26
• 239000012074 organic phase Substances 0.000 description 25
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 25
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• 238000003818 flash chromatography Methods 0.000 description 23
• 239000000843 powder Substances 0.000 description 21
• 229910000027 potassium carbonate Inorganic materials 0.000 description 19
• 239000002253 acid Substances 0.000 description 17
• 238000010992 reflux Methods 0.000 description 17
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
• 235000017557 sodium bicarbonate Nutrition 0.000 description 17
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 238000001704 evaporation Methods 0.000 description 16
• 239000003208 petroleum Substances 0.000 description 16
• 239000012071 phase Substances 0.000 description 16
• 239000011734 sodium Substances 0.000 description 16
• 229960000583 acetic acid Drugs 0.000 description 15
• 238000001816 cooling Methods 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 13
• 239000007864 aqueous solution Substances 0.000 description 13
• 230000008020 evaporation Effects 0.000 description 13
• 239000003120 macrolide antibiotic agent Substances 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• 238000002953 preparative HPLC Methods 0.000 description 13
• 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 13
• RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
• 239000003795 chemical substances by application Substances 0.000 description 12
• 239000000284 extract Substances 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 239000002808 molecular sieve Substances 0.000 description 12
• 239000000377 silicon dioxide Substances 0.000 description 12
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 12
• 239000002585 base Substances 0.000 description 11
• 125000004432 carbon atom Chemical group C* 0.000 description 11
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
• 238000001914 filtration Methods 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
• 229940002612 prodrug Drugs 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• 239000012453 solvate Substances 0.000 description 10
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 8
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
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• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• 150000003254 radicals Chemical class 0.000 description 8
• 239000001632 sodium acetate Substances 0.000 description 8
• 235000017281 sodium acetate Nutrition 0.000 description 8
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 8
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
• 239000008259 solid foam Substances 0.000 description 8
• INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 7
• 238000001035 drying Methods 0.000 description 7
• 229940099584 lactobionate Drugs 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
• 229920000858 Cyclodextrin Polymers 0.000 description 6
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 6
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• 239000004480 active ingredient Substances 0.000 description 6
• XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 6
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 6
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 6
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 6
• MVUMJYQUKKUOHO-AATRIKPKSA-N ethyl (e)-3-(dimethylamino)prop-2-enoate Chemical compound CCOC(=O)\C=C\N(C)C MVUMJYQUKKUOHO-AATRIKPKSA-N 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 6
• 229940041033 macrolides Drugs 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
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