JP4991543B2 - ジアリールシクロアルキル誘導体の製造方法 - Google Patents
ジアリールシクロアルキル誘導体の製造方法 Download PDFInfo
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- JP4991543B2 JP4991543B2 JP2007528733A JP2007528733A JP4991543B2 JP 4991543 B2 JP4991543 B2 JP 4991543B2 JP 2007528733 A JP2007528733 A JP 2007528733A JP 2007528733 A JP2007528733 A JP 2007528733A JP 4991543 B2 JP4991543 B2 JP 4991543B2
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- Prior art keywords
- compound
- cis
- formula
- alkyl
- ylmethoxy
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- 238000004519 manufacturing process Methods 0.000 title description 17
- 150000001875 compounds Chemical class 0.000 claims description 269
- -1 alkaline earth metal alkoxide Chemical group 0.000 claims description 82
- 238000000034 method Methods 0.000 claims description 74
- 238000006243 chemical reaction Methods 0.000 claims description 64
- 239000000203 mixture Substances 0.000 claims description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 50
- 125000006239 protecting group Chemical group 0.000 claims description 45
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 230000008569 process Effects 0.000 claims description 33
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 25
- 230000002378 acidificating effect Effects 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 239000002585 base Substances 0.000 claims description 20
- 239000003054 catalyst Substances 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 241001661345 Moesziomyces antarcticus Species 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 101710098554 Lipase B Proteins 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 16
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 15
- 229910052783 alkali metal Inorganic materials 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 12
- 150000001340 alkali metals Chemical class 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 239000012038 nucleophile Substances 0.000 claims description 9
- 150000001342 alkaline earth metals Chemical group 0.000 claims description 5
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 110
- 239000000243 solution Substances 0.000 description 50
- 108090001060 Lipase Proteins 0.000 description 40
- 239000004367 Lipase Substances 0.000 description 40
- 102000004882 Lipase Human genes 0.000 description 40
- 235000019421 lipase Nutrition 0.000 description 40
- 239000002904 solvent Substances 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 230000015572 biosynthetic process Effects 0.000 description 33
- 108090000790 Enzymes Proteins 0.000 description 29
- 102000004190 Enzymes Human genes 0.000 description 29
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 27
- 230000002255 enzymatic effect Effects 0.000 description 26
- 230000010933 acylation Effects 0.000 description 25
- 238000005917 acylation reaction Methods 0.000 description 25
- 239000012074 organic phase Substances 0.000 description 25
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 22
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 22
- 239000012190 activator Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 125000002252 acyl group Chemical group 0.000 description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- 239000000543 intermediate Substances 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- 230000029936 alkylation Effects 0.000 description 18
- 238000005804 alkylation reaction Methods 0.000 description 18
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- 238000000746 purification Methods 0.000 description 17
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 16
- 239000008346 aqueous phase Substances 0.000 description 16
- 239000006227 byproduct Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 15
- 230000007062 hydrolysis Effects 0.000 description 15
- 238000006460 hydrolysis reaction Methods 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 229940095102 methyl benzoate Drugs 0.000 description 14
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 14
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 13
- 239000003960 organic solvent Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 11
- 238000000926 separation method Methods 0.000 description 11
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 10
- 238000003821 enantio-separation Methods 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- UDNSKBMNXZVXKW-UHFFFAOYSA-N methyl 2-(bromomethyl)-6-methylbenzoate Chemical compound COC(=O)C1=C(C)C=CC=C1CBr UDNSKBMNXZVXKW-UHFFFAOYSA-N 0.000 description 10
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- RLMGYIOTPQVQJR-OLQVQODUSA-N (1s,3r)-cyclohexane-1,3-diol Chemical compound O[C@H]1CCC[C@@H](O)C1 RLMGYIOTPQVQJR-OLQVQODUSA-N 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 241000589513 Burkholderia cepacia Species 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- PIAZUOCNDRREHF-AOOOYVTPSA-N [(1s,3r)-3-acetyloxycyclohexyl] acetate Chemical compound CC(=O)O[C@H]1CCC[C@@H](OC(C)=O)C1 PIAZUOCNDRREHF-AOOOYVTPSA-N 0.000 description 9
- 150000007522 mineralic acids Chemical class 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- RLMGYIOTPQVQJR-UHFFFAOYSA-N cyclohexane-1,3-diol Chemical compound OC1CCCC(O)C1 RLMGYIOTPQVQJR-UHFFFAOYSA-N 0.000 description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 238000005191 phase separation Methods 0.000 description 7
- ISBNRLAQTNTMJJ-PKTZIBPZSA-N 2-methyl-6-[[(1r,3s)-3-[[5-methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]methoxy]cyclohexyl]oxymethyl]benzoic acid Chemical compound O([C@@H]1CCC[C@@H](C1)OCC=1N=C(OC=1C)C=1C=CC(C)=CC=1)CC1=CC=CC(C)=C1C(O)=O ISBNRLAQTNTMJJ-PKTZIBPZSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- BQNHLNYNOYQQSQ-UHFFFAOYSA-N 2-(bromomethyl)-6-methylbenzoyl bromide Chemical compound CC1=CC=CC(CBr)=C1C(Br)=O BQNHLNYNOYQQSQ-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 241001453380 Burkholderia Species 0.000 description 5
- 241000589516 Pseudomonas Species 0.000 description 5
- WRESCWICNKVBFZ-UHFFFAOYSA-N benzyl 2-(bromomethyl)-6-methylbenzoate Chemical compound CC1=CC=CC(CBr)=C1C(=O)OCC1=CC=CC=C1 WRESCWICNKVBFZ-UHFFFAOYSA-N 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 230000006196 deacetylation Effects 0.000 description 5
- 238000003381 deacetylation reaction Methods 0.000 description 5
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 description 5
- 210000000496 pancreas Anatomy 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- JEICKCSYNQEYKK-UHFFFAOYSA-N tert-butyl 2-(bromomethyl)-6-methylbenzoate Chemical compound CC1=CC=CC(CBr)=C1C(=O)OC(C)(C)C JEICKCSYNQEYKK-UHFFFAOYSA-N 0.000 description 5
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- PIAZUOCNDRREHF-UWVGGRQHSA-N [(1s,3s)-3-acetyloxycyclohexyl] acetate Chemical compound CC(=O)O[C@H]1CCC[C@H](OC(C)=O)C1 PIAZUOCNDRREHF-UWVGGRQHSA-N 0.000 description 4
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- 239000012455 biphasic mixture Substances 0.000 description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
- 230000020176 deacylation Effects 0.000 description 4
- 238000005947 deacylation reaction Methods 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000002531 positive electrospray ionisation time-of-flight mass spectrometry Methods 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- RLMGYIOTPQVQJR-WDSKDSINSA-N (1s,3s)-cyclohexane-1,3-diol Chemical compound O[C@H]1CCC[C@H](O)C1 RLMGYIOTPQVQJR-WDSKDSINSA-N 0.000 description 3
- 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 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 150000001733 carboxylic acid esters Chemical class 0.000 description 3
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 230000007071 enzymatic hydrolysis Effects 0.000 description 3
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 229910000000 metal hydroxide Inorganic materials 0.000 description 3
- 150000004692 metal hydroxides Chemical class 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 230000020477 pH reduction Effects 0.000 description 3
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- PIAZUOCNDRREHF-UHFFFAOYSA-N (3-acetyloxycyclohexyl) acetate Chemical compound CC(=O)OC1CCCC(OC(C)=O)C1 PIAZUOCNDRREHF-UHFFFAOYSA-N 0.000 description 2
- VWFGBAZRKXYFCO-UHFFFAOYSA-N 4-(chloromethyl)-2-(3-methoxyphenyl)-5-methyl-1,3-oxazole Chemical compound COC1=CC=CC(C=2OC(C)=C(CCl)N=2)=C1 VWFGBAZRKXYFCO-UHFFFAOYSA-N 0.000 description 2
- GVPZSTFLDSJXRT-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-fluorophenyl)-1,3-oxazole Chemical compound C1=CC(F)=CC=C1C1=NC(CCl)=CO1 GVPZSTFLDSJXRT-UHFFFAOYSA-N 0.000 description 2
- DQTOUJFUSUPWOK-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-(4-methylphenyl)-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=CC(C)=CC=2)=N1 DQTOUJFUSUPWOK-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 150000004703 alkoxides Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- XUPYJHCZDLZNFP-UHFFFAOYSA-N butyl butanoate Chemical compound CCCCOC(=O)CCC XUPYJHCZDLZNFP-UHFFFAOYSA-N 0.000 description 2
- 239000012159 carrier gas Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229920001429 chelating resin Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007257 deesterification reaction Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- UFFSXJKVKBQEHC-UHFFFAOYSA-N heptafluorobutyric anhydride Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(=O)OC(=O)C(F)(F)C(F)(F)C(F)(F)F UFFSXJKVKBQEHC-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- YPJUNDFVDDCYIH-UHFFFAOYSA-N perfluorobutyric acid Chemical compound OC(=O)C(F)(F)C(F)(F)C(F)(F)F YPJUNDFVDDCYIH-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 150000003254 radicals Chemical group 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003606 tin compounds Chemical class 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- 150000000185 1,3-diols Chemical class 0.000 description 1
- QHMVQKOXILNZQR-UHFFFAOYSA-N 1-methoxyprop-1-ene Chemical compound COC=CC QHMVQKOXILNZQR-UHFFFAOYSA-N 0.000 description 1
- VIWONCNRYPUJLL-UHFFFAOYSA-N 2-(4-fluorophenyl)-1,3-oxazole Chemical compound C1=CC(F)=CC=C1C1=NC=CO1 VIWONCNRYPUJLL-UHFFFAOYSA-N 0.000 description 1
- BKBQJEGATMJTIY-UHFFFAOYSA-N 2-(bromomethyl)benzoyl bromide Chemical class BrCC1=CC=CC=C1C(Br)=O BKBQJEGATMJTIY-UHFFFAOYSA-N 0.000 description 1
- URUKMUHHWWCNKS-UHFFFAOYSA-N 2-cyclohexyloxane Chemical compound C1CCCCC1C1OCCCC1 URUKMUHHWWCNKS-UHFFFAOYSA-N 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- 102100021851 Calbindin Human genes 0.000 description 1
- 108010031797 Candida antarctica lipase B Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 101000898082 Homo sapiens Calbindin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
- 241000196329 Marchantia polymorpha Species 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 108010084311 Novozyme 435 Proteins 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- 101001021643 Pseudozyma antarctica Lipase B Proteins 0.000 description 1
- 241000235403 Rhizomucor miehei Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KKGVEAWZDIBQMT-HTQZYQBOSA-N [(1r,3r)-3-hydroxycyclohexyl] acetate Chemical compound CC(=O)O[C@@H]1CCC[C@@H](O)C1 KKGVEAWZDIBQMT-HTQZYQBOSA-N 0.000 description 1
- KKGVEAWZDIBQMT-JGVFFNPUSA-N [(1r,3s)-3-hydroxycyclohexyl] acetate Chemical compound CC(=O)O[C@@H]1CCC[C@H](O)C1 KKGVEAWZDIBQMT-JGVFFNPUSA-N 0.000 description 1
- UKPIBFMHHUEUQR-DTORHVGOSA-N [(1s,4r)-4-acetyloxycyclopent-2-en-1-yl] acetate Chemical compound CC(=O)O[C@@H]1C[C@H](OC(C)=O)C=C1 UKPIBFMHHUEUQR-DTORHVGOSA-N 0.000 description 1
- KOOADCGQJDGAGA-UHFFFAOYSA-N [amino(dimethyl)silyl]methane Chemical compound C[Si](C)(C)N KOOADCGQJDGAGA-UHFFFAOYSA-N 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 238000006359 acetalization reaction Methods 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- WUTORDIVHQYAPT-IHLOFXLRSA-N benzyl 2-methyl-6-[[(1r,3s)-3-[[5-methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]methoxy]cyclohexyl]oxymethyl]benzoate Chemical compound O([C@@H]1CCC[C@@H](C1)OCC=1N=C(OC=1C)C=1C=CC(C)=CC=1)CC1=CC=CC(C)=C1C(=O)OCC1=CC=CC=C1 WUTORDIVHQYAPT-IHLOFXLRSA-N 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- MDQDBTCGQGXTBP-UHFFFAOYSA-N bromomethyl benzoate Chemical class BrCOC(=O)C1=CC=CC=C1 MDQDBTCGQGXTBP-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- PDXRQENMIVHKPI-UHFFFAOYSA-N cyclohexane-1,1-diol Chemical class OC1(O)CCCCC1 PDXRQENMIVHKPI-UHFFFAOYSA-N 0.000 description 1
- 150000001934 cyclohexanes Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GLVVKKSPKXTQRB-UHFFFAOYSA-N ethenyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC=C GLVVKKSPKXTQRB-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 210000000540 fraction c Anatomy 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- SRLKZPDOALSGPA-FTJBHMTQSA-N tert-butyl 2-methyl-6-[[(1r,3s)-3-[[5-methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]methoxy]cyclohexyl]oxymethyl]benzoate Chemical compound O([C@@H]1CCC[C@@H](C1)OCC=1N=C(OC=1C)C=1C=CC(C)=CC=1)CC1=CC=CC(C)=C1C(=O)OC(C)(C)C SRLKZPDOALSGPA-FTJBHMTQSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/62—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems having two or more ring systems containing condensed 1,3-oxazole rings
-
- 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
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/14—Nitrogen or oxygen as hetero atom and at least one other diverse hetero ring atom in the same ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Obesity (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004040736A DE102004040736B4 (de) | 2004-08-23 | 2004-08-23 | Verfahren zur Herstellung von Diarylcycloalkylderivaten |
| DE102004040736.3 | 2004-08-23 | ||
| PCT/EP2005/009095 WO2006021420A2 (de) | 2004-08-23 | 2005-08-23 | Verfahren zur herstellung von diarylcycloalkylderivaten |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008510761A JP2008510761A (ja) | 2008-04-10 |
| JP2008510761A5 JP2008510761A5 (enExample) | 2008-10-09 |
| JP4991543B2 true JP4991543B2 (ja) | 2012-08-01 |
Family
ID=35745474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007528733A Expired - Fee Related JP4991543B2 (ja) | 2004-08-23 | 2005-08-23 | ジアリールシクロアルキル誘導体の製造方法 |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US7803950B2 (enExample) |
| EP (1) | EP1786913B1 (enExample) |
| JP (1) | JP4991543B2 (enExample) |
| KR (1) | KR20070048741A (enExample) |
| CN (1) | CN101014714B (enExample) |
| AR (1) | AR053760A1 (enExample) |
| AT (1) | ATE520785T1 (enExample) |
| AU (1) | AU2005276642B2 (enExample) |
| BR (1) | BRPI0514000A (enExample) |
| CA (1) | CA2578342A1 (enExample) |
| CY (1) | CY1112080T1 (enExample) |
| DE (1) | DE102004040736B4 (enExample) |
| DK (1) | DK1786913T3 (enExample) |
| ES (1) | ES2371762T3 (enExample) |
| IL (1) | IL181339A0 (enExample) |
| MA (1) | MA28796B1 (enExample) |
| MX (1) | MX2007001872A (enExample) |
| NO (1) | NO20071316L (enExample) |
| NZ (1) | NZ553602A (enExample) |
| PL (1) | PL1786913T3 (enExample) |
| PT (1) | PT1786913E (enExample) |
| RU (1) | RU2414459C2 (enExample) |
| SI (1) | SI1786913T1 (enExample) |
| TW (1) | TW200621734A (enExample) |
| UY (1) | UY29082A1 (enExample) |
| WO (1) | WO2006021420A2 (enExample) |
| ZA (1) | ZA200700635B (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050232972A1 (en) * | 2004-04-15 | 2005-10-20 | Steven Odrich | Drug delivery via punctal plug |
| CN101381302B (zh) * | 2007-09-07 | 2013-04-03 | 上海睿智化学研究有限公司 | 2-溴甲基-6-甲基苯甲酰氯/溴的制备方法 |
| ES2601852T3 (es) * | 2008-01-25 | 2017-02-16 | Xenoport, Inc. | Forma cristalina de sales de calcio de ácidos (3S)-aminometil-5-metil-hexanoicos y métodos de uso |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5728899A (en) * | 1995-03-27 | 1998-03-17 | Hoechst Marion Roussel Inc. | Preparation of cis-4-O-protected-2-cyclopentenol derivatives |
| US6884812B2 (en) * | 2001-08-31 | 2005-04-26 | Aventis Pharma Deutschland Gmbh | Diarylcycloalkyl derivatives, processes for their preparation and their use as pharmaceuticals |
| AU2002333456B2 (en) * | 2001-08-31 | 2008-07-17 | Sanofi-Aventis Deutschland Gmbh | Diaryl cycloalkyl derivatives, method for producing the same and the use thereof as PPAR activators |
| JP2005529077A (ja) * | 2002-02-25 | 2005-09-29 | イーライ・リリー・アンド・カンパニー | ペルオキシソーム増殖因子活性化受容体調節物質 |
| US7094795B2 (en) * | 2003-02-27 | 2006-08-22 | Sanofi-Aventis Deutschland Gmbh | Process for preparing the enantiomeric forms of cis-configured 1,3-cyclohexanediol derivatives |
| DE10308353A1 (de) * | 2003-02-27 | 2004-12-02 | Aventis Pharma Deutschland Gmbh | Diarylcycloalkylderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE10308350B4 (de) * | 2003-02-27 | 2006-06-01 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung der enantiomeren Formen von cis-konfigurierten 1,3-Cyclohexandiol-Derivaten |
| EP1689874A1 (fr) * | 2003-10-22 | 2006-08-16 | Rhodia Chimie | Procede de fabrication de compose comprenant un groupement hydroxyle libre et un groupement hydroxyle protege par une fonction ester par reaction enzymatique |
| DE102004038403B4 (de) * | 2004-08-07 | 2006-08-31 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung der enantiomeren Formen von cis-konfigurierten 3-Hydroxycyclohexancarbonsäure-Derivaten |
-
2004
- 2004-08-23 DE DE102004040736A patent/DE102004040736B4/de not_active Expired - Fee Related
-
2005
- 2005-08-22 AR ARP050103522A patent/AR053760A1/es not_active Application Discontinuation
- 2005-08-22 TW TW094128546A patent/TW200621734A/zh unknown
- 2005-08-23 KR KR1020077004449A patent/KR20070048741A/ko not_active Ceased
- 2005-08-23 RU RU2007110644/04A patent/RU2414459C2/ru not_active IP Right Cessation
- 2005-08-23 DK DK05782434.4T patent/DK1786913T3/da active
- 2005-08-23 SI SI200531403T patent/SI1786913T1/sl unknown
- 2005-08-23 EP EP05782434A patent/EP1786913B1/de not_active Expired - Lifetime
- 2005-08-23 CA CA002578342A patent/CA2578342A1/en not_active Abandoned
- 2005-08-23 AU AU2005276642A patent/AU2005276642B2/en not_active Ceased
- 2005-08-23 AT AT05782434T patent/ATE520785T1/de active
- 2005-08-23 PL PL05782434T patent/PL1786913T3/pl unknown
- 2005-08-23 ES ES05782434T patent/ES2371762T3/es not_active Expired - Lifetime
- 2005-08-23 UY UY29082A patent/UY29082A1/es unknown
- 2005-08-23 BR BRPI0514000-5A patent/BRPI0514000A/pt not_active IP Right Cessation
- 2005-08-23 CN CN200580028364XA patent/CN101014714B/zh not_active Expired - Fee Related
- 2005-08-23 NZ NZ553602A patent/NZ553602A/en not_active IP Right Cessation
- 2005-08-23 WO PCT/EP2005/009095 patent/WO2006021420A2/de not_active Ceased
- 2005-08-23 JP JP2007528733A patent/JP4991543B2/ja not_active Expired - Fee Related
- 2005-08-23 PT PT05782434T patent/PT1786913E/pt unknown
- 2005-08-23 MX MX2007001872A patent/MX2007001872A/es active IP Right Grant
-
2007
- 2007-01-23 ZA ZA200700635A patent/ZA200700635B/xx unknown
- 2007-02-08 MA MA29674A patent/MA28796B1/fr unknown
- 2007-02-14 IL IL181339A patent/IL181339A0/en unknown
- 2007-02-20 US US11/676,721 patent/US7803950B2/en not_active Expired - Fee Related
- 2007-03-12 NO NO20071316A patent/NO20071316L/no not_active Application Discontinuation
- 2007-10-31 US US11/930,244 patent/US20080051583A1/en not_active Abandoned
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2011
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