PT1399402E - Derivados intermédios do grupo halofenilo e sua utilização em um processo para a preparação de derivados de azole - Google Patents
Derivados intermédios do grupo halofenilo e sua utilização em um processo para a preparação de derivados de azole Download PDFInfo
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- PT1399402E PT1399402E PT02754691T PT02754691T PT1399402E PT 1399402 E PT1399402 E PT 1399402E PT 02754691 T PT02754691 T PT 02754691T PT 02754691 T PT02754691 T PT 02754691T PT 1399402 E PT1399402 E PT 1399402E
- Authority
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- Prior art keywords
- mmol
- methyl
- sup
- ethyl acetate
- solution
- Prior art date
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- 125000005059 halophenyl group Chemical group 0.000 title claims abstract 6
- 150000007980 azole derivatives Chemical class 0.000 title abstract description 6
- 238000004519 manufacturing process Methods 0.000 title abstract 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims abstract description 3
- -1 2,5-difluoro-phenyl Chemical group 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 7
- JRBXDSNLMNJVKJ-QPUJVOFHSA-N (2r,3s)-1-chloro-2-(2,4-difluorophenyl)-3-methylpent-4-yn-2-ol Chemical compound C#C[C@H](C)[C@](O)(CCl)C1=CC=C(F)C=C1F JRBXDSNLMNJVKJ-QPUJVOFHSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 abstract description 3
- 208000031888 Mycoses Diseases 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- 230000009885 systemic effect Effects 0.000 abstract description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 239000012071 phase Substances 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 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 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 6
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 6
- WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- ZXTGFMXFEMKHHX-RXMQYKEDSA-N [(2r)-but-3-yn-2-yl] methanesulfonate Chemical compound C#C[C@@H](C)OS(C)(=O)=O ZXTGFMXFEMKHHX-RXMQYKEDSA-N 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- HJWDDTDVBUFTCP-UHFFFAOYSA-N 2-chloro-1-(2,5-difluorophenyl)ethanone Chemical compound FC1=CC=C(F)C(C(=O)CCl)=C1 HJWDDTDVBUFTCP-UHFFFAOYSA-N 0.000 description 4
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 4
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 229940121375 antifungal agent Drugs 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- UWVOPVUWKIHGRF-ISVAXAHUSA-N (2r,3r)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1,2,4-triazol-1-yl)butanethioamide Chemical compound C([C@@](O)([C@H](C(N)=S)C)C=1C(=CC=C(F)C=1)F)N1C=NC=N1 UWVOPVUWKIHGRF-ISVAXAHUSA-N 0.000 description 2
- CHIBRGXNZYRDAF-QPUJVOFHSA-N (2r,3s)-1-chloro-2-(2,5-difluorophenyl)-3-methylpent-4-yn-2-ol Chemical compound C#C[C@H](C)[C@](O)(CCl)C1=CC(F)=CC=C1F CHIBRGXNZYRDAF-QPUJVOFHSA-N 0.000 description 2
- NSPMIYGKQJPBQR-CVMUNTFWSA-N 1h-1,2,4-triazole Chemical group [13CH]=1[15N]=[13CH][15NH][15N]=1 NSPMIYGKQJPBQR-CVMUNTFWSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 2
- GKPOMITUDGXOSB-SCSAIBSYSA-N (2r)-but-3-yn-2-ol Chemical compound C[C@@H](O)C#C GKPOMITUDGXOSB-SCSAIBSYSA-N 0.000 description 1
- ARTKJILLNLYJNZ-ISVAXAHUSA-N (2r,3r)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1,2,4-triazol-1-yl)butanamide Chemical compound C([C@@](O)([C@H](C(N)=O)C)C=1C(=CC=C(F)C=1)F)N1C=NC=N1 ARTKJILLNLYJNZ-ISVAXAHUSA-N 0.000 description 1
- SYSUFNUKZJVPBI-NOZJJQNGSA-N (2r,3r)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1,2,4-triazol-1-yl)butanenitrile Chemical compound C([C@@](O)([C@@H](C#N)C)C=1C(=CC=C(F)C=1)F)N1C=NC=N1 SYSUFNUKZJVPBI-NOZJJQNGSA-N 0.000 description 1
- VROXYWTWIYBPOA-IINYFYTJSA-N (2r,3s)-2-(2,4-difluorophenyl)-3-methyl-1-(1,2,4-triazol-1-yl)pent-4-yn-2-ol Chemical compound C([C@@](O)([C@H](C#C)C)C=1C(=CC(F)=CC=1)F)N1C=NC=N1 VROXYWTWIYBPOA-IINYFYTJSA-N 0.000 description 1
- IPVIQHWONKNMPV-IINYFYTJSA-N (2r,3s)-2-(2,5-difluorophenyl)-3-methyl-1-(1,2,4-triazol-1-yl)pent-4-yn-2-ol Chemical compound C([C@@](O)([C@H](C#C)C)C=1C(=CC=C(F)C=1)F)N1C=NC=N1 IPVIQHWONKNMPV-IINYFYTJSA-N 0.000 description 1
- BLVZJTXQMVLLME-ISVAXAHUSA-N (3r,4r)-4-(2,5-difluorophenyl)-3-methyl-4-(1,2,4-triazol-1-ylmethyl)oxetan-2-one Chemical compound C[C@H]1C(=O)O[C@]1(C=1C(=CC=C(F)C=1)F)CN1N=CN=C1 BLVZJTXQMVLLME-ISVAXAHUSA-N 0.000 description 1
- QUGUFLJIAFISSW-UHFFFAOYSA-N 1,4-difluorobenzene Chemical compound FC1=CC=C(F)C=C1 QUGUFLJIAFISSW-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VTJMSIIXXKNIDJ-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-methylbutyric acid Chemical compound CC(C)C(C(O)=O)C1=CC=C(Cl)C=C1 VTJMSIIXXKNIDJ-UHFFFAOYSA-N 0.000 description 1
- MZLCDVZIUBLZRI-UHFFFAOYSA-N 2-(triazol-1-yl)butanamide Chemical compound CCC(C(N)=O)N1C=CN=N1 MZLCDVZIUBLZRI-UHFFFAOYSA-N 0.000 description 1
- DPFHFGLYTYYQFG-UHFFFAOYSA-N 2-(triazol-1-yl)butanoic acid Chemical compound CCC(C(O)=O)N1C=CN=N1 DPFHFGLYTYYQFG-UHFFFAOYSA-N 0.000 description 1
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 1
- LJANCPRIUMHGJE-UHFFFAOYSA-N 4-(2-bromoacetyl)benzonitrile Chemical compound BrCC(=O)C1=CC=C(C#N)C=C1 LJANCPRIUMHGJE-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- UYJXRRSPUVSSMN-UHFFFAOYSA-P ammonium sulfide Chemical compound [NH4+].[NH4+].[S-2] UYJXRRSPUVSSMN-UHFFFAOYSA-P 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 125000003180 beta-lactone group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- IRDLUHRVLVEUHA-UHFFFAOYSA-N diethyl dithiophosphate Chemical compound CCOP(S)(=S)OCC IRDLUHRVLVEUHA-UHFFFAOYSA-N 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical compound OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- DDFOUSQFMYRUQK-RCDICMHDSA-N isavuconazole Chemical compound C=1SC([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC=C(F)C=2)F)=NC=1C1=CC=C(C#N)C=C1 DDFOUSQFMYRUQK-RCDICMHDSA-N 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- OPAHEYNNJWPQPX-RCDICMHDSA-N ravuconazole Chemical compound C=1SC([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=1C1=CC=C(C#N)C=C1 OPAHEYNNJWPQPX-RCDICMHDSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 229910001925 ruthenium oxide Inorganic materials 0.000 description 1
- ZFMWJMXYXKJRFT-UHFFFAOYSA-N ruthenium(4+) hydrate Chemical compound O.[Ru+4] ZFMWJMXYXKJRFT-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005980 thioamidation reaction Methods 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/40—Halogenated unsaturated alcohols
- C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
- C07C33/48—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts with unsaturation outside the aromatic rings
- C07C33/483—Monocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01115355 | 2001-06-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1399402E true PT1399402E (pt) | 2010-11-30 |
Family
ID=8177821
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT02754691T PT1399402E (pt) | 2001-06-26 | 2002-06-17 | Derivados intermédios do grupo halofenilo e sua utilização em um processo para a preparação de derivados de azole |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US7115643B2 (enExample) |
| EP (1) | EP1399402B1 (enExample) |
| JP (1) | JP4125672B2 (enExample) |
| KR (1) | KR100898887B1 (enExample) |
| CN (1) | CN1223564C (enExample) |
| AT (1) | ATE482920T1 (enExample) |
| AU (1) | AU2002321068B2 (enExample) |
| BR (1) | BR0210701A (enExample) |
| CA (1) | CA2449800C (enExample) |
| CY (1) | CY1111510T1 (enExample) |
| DE (1) | DE60237817D1 (enExample) |
| DK (1) | DK1399402T3 (enExample) |
| ES (1) | ES2349918T3 (enExample) |
| MX (1) | MXPA03010914A (enExample) |
| PT (1) | PT1399402E (enExample) |
| WO (1) | WO2003002498A1 (enExample) |
| ZA (1) | ZA200309101B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8207352B2 (en) * | 2009-10-08 | 2012-06-26 | Drug Process Licensing Associates LLC | Process for the manufacture of enantiomerically pure antifungal azoles as ravuconazole and isavuconazole |
| HUE031679T2 (en) | 2012-08-07 | 2017-07-28 | Basilea Pharmaceutica Ag | Process for the preparation of isavuconazole or ravuconazole |
| US20140371179A1 (en) * | 2013-06-13 | 2014-12-18 | Professional Compounding Centers Of America | Methods and Compositions for Treating Esophageal Diseases |
| CN105801500B (zh) * | 2014-12-31 | 2018-08-24 | 四川科伦药物研究院有限公司 | 拆分艾沙康唑中间化合物消旋体的方法 |
| CN115611822B (zh) * | 2022-10-12 | 2023-09-19 | 四川澄华生物科技有限公司 | 艾沙康唑中间体的制备方法 |
| CN116478103B (zh) * | 2023-03-24 | 2025-07-25 | 四川澄华生物科技有限公司 | 一种拆分艾沙康唑中间体4的方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5395942A (en) * | 1980-06-02 | 1995-03-07 | Zeneca Limited | Heterocyclic compounds |
| DE3942790A1 (de) * | 1989-12-23 | 1991-06-27 | Hoechst Ag | Verfahren zur herstellung von 2-(4-chlorphenyl)-3-methylbuttersaeure |
| GB9107055D0 (en) * | 1991-04-04 | 1991-05-22 | Pfizer Ltd | Triazole antifungal agents |
| JP3471831B2 (ja) * | 1991-12-09 | 2003-12-02 | 富山化学工業株式会社 | 新規なトリアゾール誘導体およびその塩 |
| ES2062941B1 (es) * | 1993-03-15 | 1995-10-01 | Uriach & Cia Sa J | Nuevos derivados de azol activos por via oral. |
| NZ270418A (en) | 1994-02-07 | 1997-09-22 | Eisai Co Ltd | Polycyclic triazole & imidazole derivatives, antifungal compositions |
-
2002
- 2002-06-17 AU AU2002321068A patent/AU2002321068B2/en not_active Ceased
- 2002-06-17 EP EP02754691A patent/EP1399402B1/en not_active Expired - Lifetime
- 2002-06-17 CN CNB028126416A patent/CN1223564C/zh not_active Expired - Lifetime
- 2002-06-17 PT PT02754691T patent/PT1399402E/pt unknown
- 2002-06-17 MX MXPA03010914A patent/MXPA03010914A/es active IP Right Grant
- 2002-06-17 WO PCT/EP2002/006644 patent/WO2003002498A1/en not_active Ceased
- 2002-06-17 DE DE60237817T patent/DE60237817D1/de not_active Expired - Lifetime
- 2002-06-17 CA CA002449800A patent/CA2449800C/en not_active Expired - Fee Related
- 2002-06-17 AT AT02754691T patent/ATE482920T1/de active
- 2002-06-17 KR KR1020037016987A patent/KR100898887B1/ko not_active Expired - Fee Related
- 2002-06-17 BR BR0210701-5A patent/BR0210701A/pt not_active IP Right Cessation
- 2002-06-17 ES ES02754691T patent/ES2349918T3/es not_active Expired - Lifetime
- 2002-06-17 DK DK02754691.0T patent/DK1399402T3/da active
- 2002-06-17 US US10/481,654 patent/US7115643B2/en not_active Expired - Lifetime
- 2002-06-17 JP JP2003508683A patent/JP4125672B2/ja not_active Expired - Lifetime
-
2003
- 2003-11-21 ZA ZA2003/09101A patent/ZA200309101B/en unknown
-
2010
- 2010-12-20 CY CY20101101172T patent/CY1111510T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1223564C (zh) | 2005-10-19 |
| US7115643B2 (en) | 2006-10-03 |
| DK1399402T3 (da) | 2010-11-15 |
| KR20040012982A (ko) | 2004-02-11 |
| EP1399402A1 (en) | 2004-03-24 |
| DE60237817D1 (de) | 2010-11-11 |
| JP4125672B2 (ja) | 2008-07-30 |
| ATE482920T1 (de) | 2010-10-15 |
| JP2004535444A (ja) | 2004-11-25 |
| BR0210701A (pt) | 2004-07-20 |
| WO2003002498A1 (en) | 2003-01-09 |
| AU2002321068B2 (en) | 2007-11-15 |
| KR100898887B1 (ko) | 2009-05-21 |
| US20040176432A1 (en) | 2004-09-09 |
| CN1520390A (zh) | 2004-08-11 |
| EP1399402B1 (en) | 2010-09-29 |
| CA2449800C (en) | 2009-09-29 |
| ES2349918T3 (es) | 2011-01-13 |
| CY1111510T1 (el) | 2015-08-05 |
| MXPA03010914A (es) | 2004-02-17 |
| CA2449800A1 (en) | 2003-01-09 |
| ZA200309101B (en) | 2005-03-30 |
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