AU2012335280B2 - Process for the preparation of beta-C-aryl glucosides - Google Patents
Process for the preparation of beta-C-aryl glucosides Download PDFInfo
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- AU2012335280B2 AU2012335280B2 AU2012335280A AU2012335280A AU2012335280B2 AU 2012335280 B2 AU2012335280 B2 AU 2012335280B2 AU 2012335280 A AU2012335280 A AU 2012335280A AU 2012335280 A AU2012335280 A AU 2012335280A AU 2012335280 B2 AU2012335280 B2 AU 2012335280B2
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- 238000000034 method Methods 0.000 title claims abstract description 147
- 230000008569 process Effects 0.000 title claims abstract description 78
- 238000002360 preparation method Methods 0.000 title claims description 22
- 229930182478 glucoside Natural products 0.000 title description 23
- 150000001875 compounds Chemical class 0.000 claims description 240
- 239000000203 mixture Substances 0.000 claims description 213
- 238000006254 arylation reaction Methods 0.000 claims description 208
- -1 aryl compound Chemical class 0.000 claims description 149
- 239000002904 solvent Substances 0.000 claims description 122
- 125000003118 aryl group Chemical group 0.000 claims description 111
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 75
- 125000006239 protecting group Chemical group 0.000 claims description 71
- 239000002841 Lewis acid Substances 0.000 claims description 53
- 229910052782 aluminium Inorganic materials 0.000 claims description 53
- 150000007517 lewis acids Chemical class 0.000 claims description 50
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 150000004820 halides Chemical class 0.000 claims description 41
- 239000002585 base Substances 0.000 claims description 39
- 229910052751 metal Inorganic materials 0.000 claims description 38
- 239000002184 metal Substances 0.000 claims description 37
- 150000001450 anions Chemical class 0.000 claims description 25
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 238000004519 manufacturing process Methods 0.000 claims description 21
- 230000000707 stereoselective effect Effects 0.000 claims description 21
- 229910052796 boron Inorganic materials 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 18
- 239000002879 Lewis base Substances 0.000 claims description 17
- 150000001768 cations Chemical class 0.000 claims description 15
- 150000007527 lewis bases Chemical class 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 239000006227 byproduct Substances 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 claims description 14
- 150000004703 alkoxides Chemical class 0.000 claims description 13
- 150000007942 carboxylates Chemical class 0.000 claims description 13
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 12
- 229910052752 metalloid Inorganic materials 0.000 claims description 12
- 150000002738 metalloids Chemical class 0.000 claims description 12
- 239000011777 magnesium Substances 0.000 claims description 11
- 150000002739 metals Chemical class 0.000 claims description 11
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000000654 additive Substances 0.000 claims description 10
- 229910052744 lithium Inorganic materials 0.000 claims description 10
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 10
- 238000000746 purification Methods 0.000 claims description 10
- 229910052749 magnesium Inorganic materials 0.000 claims description 9
- 229910052755 nonmetal Inorganic materials 0.000 claims description 9
- 229940031826 phenolate Drugs 0.000 claims description 9
- 150000003871 sulfonates Chemical class 0.000 claims description 9
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 7
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 7
- 150000002170 ethers Chemical class 0.000 claims description 7
- 229910052747 lanthanoid Inorganic materials 0.000 claims description 7
- 150000002602 lanthanoids Chemical class 0.000 claims description 7
- 150000002825 nitriles Chemical class 0.000 claims description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001502 aryl halides Chemical class 0.000 claims description 6
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 6
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000005841 biaryl group Chemical group 0.000 claims 5
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 3
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 2
- 150000002900 organolithium compounds Chemical class 0.000 claims 2
- 239000007818 Grignard reagent Substances 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 150000003841 chloride salts Chemical group 0.000 claims 1
- 150000005171 halobenzenes Chemical class 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 125000002306 tributylsilyl group Chemical group C(CCC)[Si](CCCC)(CCCC)* 0.000 claims 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 173
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 160
- 239000000243 solution Substances 0.000 description 133
- 238000006243 chemical reaction Methods 0.000 description 98
- 230000015572 biosynthetic process Effects 0.000 description 97
- 238000003786 synthesis reaction Methods 0.000 description 96
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 82
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 239000000047 product Substances 0.000 description 63
- TWNIBLMWSKIRAT-GASJEMHNSA-N (1r,2s,3s,4r)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2COC1O2 TWNIBLMWSKIRAT-GASJEMHNSA-N 0.000 description 52
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 101150041968 CDC13 gene Proteins 0.000 description 47
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 44
- 150000002148 esters Chemical group 0.000 description 42
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 42
- 238000004458 analytical method Methods 0.000 description 33
- 238000009835 boiling Methods 0.000 description 33
- 238000010268 HPLC based assay Methods 0.000 description 32
- 238000005481 NMR spectroscopy Methods 0.000 description 32
- 239000003446 ligand Substances 0.000 description 31
- 230000002829 reductive effect Effects 0.000 description 31
- 238000003756 stirring Methods 0.000 description 25
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 21
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 21
- 230000003647 oxidation Effects 0.000 description 20
- 238000007254 oxidation reaction Methods 0.000 description 20
- 239000000126 substance Substances 0.000 description 20
- 150000008131 glucosides Chemical class 0.000 description 19
- 239000005909 Kieselgur Substances 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 238000007792 addition Methods 0.000 description 18
- 238000001816 cooling Methods 0.000 description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
- 238000007086 side reaction Methods 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- 238000010511 deprotection reaction Methods 0.000 description 16
- NIXOIRLDFIPNLJ-UHFFFAOYSA-M magnesium;benzene;bromide Chemical compound [Mg+2].[Br-].C1=CC=[C-]C=C1 NIXOIRLDFIPNLJ-UHFFFAOYSA-M 0.000 description 16
- 229940002612 prodrug Drugs 0.000 description 16
- 239000000651 prodrug Substances 0.000 description 16
- 230000009257 reactivity Effects 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 125000004429 atom Chemical group 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- 125000000837 carbohydrate group Chemical group 0.000 description 13
- 238000010438 heat treatment Methods 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 12
- 238000013459 approach Methods 0.000 description 12
- 230000005595 deprotonation Effects 0.000 description 12
- 238000010537 deprotonation reaction Methods 0.000 description 12
- 229960001031 glucose Drugs 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- 238000006478 transmetalation reaction Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 102100020888 Sodium/glucose cotransporter 2 Human genes 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 11
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 11
- 125000005621 boronate group Chemical group 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000008103 glucose Substances 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 108091006269 SLC5A2 Proteins 0.000 description 10
- 235000014633 carbohydrates Nutrition 0.000 description 10
- 239000012065 filter cake Substances 0.000 description 10
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 10
- 125000002524 organometallic group Chemical group 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
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- 241000894007 species Species 0.000 description 9
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 8
- 238000001437 electrospray ionisation time-of-flight quadrupole detection Methods 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 229960001713 canagliflozin Drugs 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
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- 125000000524 functional group Chemical group 0.000 description 7
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- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 6
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- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 6
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- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 6
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- 239000003960 organic solvent Substances 0.000 description 6
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- 238000010626 work up procedure Methods 0.000 description 6
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- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
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- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
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- 238000011161 development Methods 0.000 description 5
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- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 5
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- 229910052745 lead Inorganic materials 0.000 description 1
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- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 1
- KCTBOHUTRYYLJA-UHFFFAOYSA-N lithium;2h-furan-2-ide Chemical compound [Li+].C=1C=[C-]OC=1 KCTBOHUTRYYLJA-UHFFFAOYSA-N 0.000 description 1
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- MCVFFRWZNYZUIJ-UHFFFAOYSA-M lithium;trifluoromethanesulfonate Chemical compound [Li+].[O-]S(=O)(=O)C(F)(F)F MCVFFRWZNYZUIJ-UHFFFAOYSA-M 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- JOWQNXIISCPKBK-UHFFFAOYSA-M magnesium;1,3,5-trimethylbenzene-6-ide;bromide Chemical compound [Mg+2].[Br-].CC1=CC(C)=[C-]C(C)=C1 JOWQNXIISCPKBK-UHFFFAOYSA-M 0.000 description 1
- HTJPDOPKPWUNBX-UHFFFAOYSA-M magnesium;2h-thiophen-2-ide;bromide Chemical compound [Mg+2].[Br-].C=1C=[C-]SC=1 HTJPDOPKPWUNBX-UHFFFAOYSA-M 0.000 description 1
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
- RBWRWAUAVRMBAC-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=[C-]C=C1 RBWRWAUAVRMBAC-UHFFFAOYSA-M 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
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- 125000002950 monocyclic group Chemical group 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
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- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 125000005492 nosylate group Chemical group 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000006464 oxidative addition reaction Methods 0.000 description 1
- 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 1
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- DLRJIFUOBPOJNS-UHFFFAOYSA-N phenetole Chemical compound CCOC1=CC=CC=C1 DLRJIFUOBPOJNS-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- JAMNHZBIQDNHMM-UHFFFAOYSA-N pivalonitrile Chemical compound CC(C)(C)C#N JAMNHZBIQDNHMM-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910052699 polonium Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 125000002577 pseudohalo group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
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- 238000012552 review Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
- 150000004819 silanols Chemical class 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- 229910052714 tellurium Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WAGFXJQAIZNSEQ-UHFFFAOYSA-M tetraphenylphosphonium chloride Chemical compound [Cl-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WAGFXJQAIZNSEQ-UHFFFAOYSA-M 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- OPSWAWSNPREEFQ-UHFFFAOYSA-K triphenoxyalumane Chemical compound [Al+3].[O-]C1=CC=CC=C1.[O-]C1=CC=CC=C1.[O-]C1=CC=CC=C1 OPSWAWSNPREEFQ-UHFFFAOYSA-K 0.000 description 1
- WSITXTIRYQMZHM-UHFFFAOYSA-N tris(4-methylphenyl)alumane Chemical compound C1=CC(C)=CC=C1[Al](C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 WSITXTIRYQMZHM-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000008096 xylene Chemical class 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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
- C07D309/10—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Saccharide Compounds (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161556780P | 2011-11-07 | 2011-11-07 | |
| US61/556,780 | 2011-11-07 | ||
| US201261661793P | 2012-06-19 | 2012-06-19 | |
| US61/661,793 | 2012-06-19 | ||
| PCT/IB2012/002894 WO2013068850A2 (en) | 2011-11-07 | 2012-11-07 | PROCESS FOR THE PREPARATION OF β-C-ARYL GLUCOSIDES |
Publications (2)
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| AU2012335280A1 AU2012335280A1 (en) | 2014-05-22 |
| AU2012335280B2 true AU2012335280B2 (en) | 2016-09-29 |
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| AU2012335280A Ceased AU2012335280B2 (en) | 2011-11-07 | 2012-11-07 | Process for the preparation of beta-C-aryl glucosides |
Country Status (11)
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557894A (zh) * | 2013-10-18 | 2015-04-29 | 上海信谊药厂有限公司 | 坎格列汀晶型及其制备方法 |
| TWI592418B (zh) * | 2014-04-11 | 2017-07-21 | 台灣神隆股份有限公司 | β－Ｃ－芳基葡萄糖苷之製造方法 |
| CN105017237A (zh) * | 2014-04-29 | 2015-11-04 | 嘉实（湖南）医药科技有限公司 | 一种卡格列净的制备工艺 |
| EP2947077A1 (en) | 2014-05-19 | 2015-11-25 | LEK Pharmaceuticals d.d. | Stereoselective synthesis of intermediates in the preparation of ß-C-arylglucosides |
| US10370365B2 (en) | 2015-09-16 | 2019-08-06 | Optimus Drugs (P) Limited | Process for the preparation of Canagliflozin |
| CN105294624B (zh) * | 2015-11-16 | 2018-01-12 | 山东罗欣药业集团股份有限公司 | 一种达格列净的制备方法 |
| CN105486767B (zh) * | 2015-12-03 | 2018-03-13 | 上海应用技术学院 | 一种达格列净及其α‑异构体的分离方法 |
| CN105541815B (zh) * | 2015-12-24 | 2018-07-13 | 寿光富康制药有限公司 | 一种卡格列净的制备方法 |
| EP4114365A1 (en) | 2020-03-05 | 2023-01-11 | KRKA, d.d., Novo mesto | Pharmaceutical composition comprising sglt2 inhibitor |
| WO2021245253A1 (en) | 2020-06-05 | 2021-12-09 | Krka, D.D., Novo Mesto | Preparation of highly pure amorphous dapagliflozin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7847074B2 (en) * | 2005-09-15 | 2010-12-07 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted (ethynyl-benzyl)-benzene derivatives and intermediates thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5872599A (ja) * | 1981-10-27 | 1983-04-30 | Kanto Ishi Pharma Co Ltd | 複合糖質誘導体 |
| WO2004063209A2 (en) * | 2003-01-03 | 2004-07-29 | Bristol-Myers Squibb Company | Methods of producing c-aryl glucoside sglt2 inhibitors |
| EP2504346A1 (en) | 2009-11-24 | 2012-10-03 | South African Medical Research Council | Method for the synthesis of aspalathin and analogues thereof |
-
2012
- 2012-11-07 JP JP2014539427A patent/JP6144686B2/ja not_active Expired - Fee Related
- 2012-11-07 TW TW101141390A patent/TWI488861B/zh not_active IP Right Cessation
- 2012-11-07 AU AU2012335280A patent/AU2012335280B2/en not_active Ceased
- 2012-11-07 WO PCT/IB2012/002894 patent/WO2013068850A2/en active Application Filing
- 2012-11-07 IN IN4050CHN2014 patent/IN2014CN04050A/en unknown
- 2012-11-07 BR BR112014010997A patent/BR112014010997A2/pt not_active Application Discontinuation
- 2012-11-07 KR KR1020147015420A patent/KR101756772B1/ko not_active Expired - Fee Related
- 2012-11-07 CA CA2854591A patent/CA2854591A1/en not_active Abandoned
- 2012-11-07 EP EP12847376.6A patent/EP2776449B1/en not_active Not-in-force
- 2012-11-07 CN CN201280054691.2A patent/CN103974964B/zh not_active Expired - Fee Related
-
2014
- 2014-05-01 IL IL232418A patent/IL232418A/en not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7847074B2 (en) * | 2005-09-15 | 2010-12-07 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted (ethynyl-benzyl)-benzene derivatives and intermediates thereof |
Non-Patent Citations (1)
| Title |
|---|
| OGURA H. et al, Nucleic Acid Chem., 1991, 4, 109-112 * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20140089427A (ko) | 2014-07-14 |
| WO2013068850A3 (en) | 2013-08-22 |
| TW201335175A (zh) | 2013-09-01 |
| CN103974964B (zh) | 2016-03-23 |
| BR112014010997A2 (pt) | 2017-06-06 |
| IN2014CN04050A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-07-10 |
| EP2776449B1 (en) | 2017-08-02 |
| WO2013068850A8 (en) | 2013-10-10 |
| WO2013068850A2 (en) | 2013-05-16 |
| TWI488861B (zh) | 2015-06-21 |
| CN103974964A (zh) | 2014-08-06 |
| IL232418A0 (en) | 2014-06-30 |
| EP2776449A2 (en) | 2014-09-17 |
| AU2012335280A1 (en) | 2014-05-22 |
| KR101756772B1 (ko) | 2017-07-26 |
| IL232418A (en) | 2016-10-31 |
| JP2014532690A (ja) | 2014-12-08 |
| EP2776449A4 (en) | 2015-10-07 |
| CA2854591A1 (en) | 2013-05-16 |
| JP6144686B2 (ja) | 2017-06-07 |
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