DK3077355T3 - Ny fremgangsmåde til syntese af 7-methoxy-napthalen-1-carbaldehyd og anvendelse deraf i syntese af agomelatin - Google Patents
Ny fremgangsmåde til syntese af 7-methoxy-napthalen-1-carbaldehyd og anvendelse deraf i syntese af agomelatin Download PDFInfo
- Publication number
- DK3077355T3 DK3077355T3 DK14821796.1T DK14821796T DK3077355T3 DK 3077355 T3 DK3077355 T3 DK 3077355T3 DK 14821796 T DK14821796 T DK 14821796T DK 3077355 T3 DK3077355 T3 DK 3077355T3
- Authority
- DK
- Denmark
- Prior art keywords
- formula
- compound
- synthesis
- conversion
- industrial synthesis
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 36
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 92
- 230000008569 process Effects 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- YJYPHIXNFHFHND-UHFFFAOYSA-N agomelatine Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(OC)=CC=C21 YJYPHIXNFHFHND-UHFFFAOYSA-N 0.000 claims description 15
- 229960002629 agomelatine Drugs 0.000 claims description 14
- 229910052723 transition metal Inorganic materials 0.000 claims description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- 150000003624 transition metals Chemical class 0.000 claims description 10
- 239000003638 chemical reducing agent Substances 0.000 claims description 8
- 238000006392 deoxygenation reaction Methods 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 7
- UNFNRIIETORURP-UHFFFAOYSA-N 7-methoxynaphthalen-2-ol Chemical compound C1=CC(O)=CC2=CC(OC)=CC=C21 UNFNRIIETORURP-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 238000005694 sulfonylation reaction Methods 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 4
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 3
- 238000000354 decomposition reaction Methods 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 150000002940 palladium Chemical class 0.000 claims description 3
- 125000005425 toluyl group Chemical group 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- JHRWWRDRBPCWTF-OLQVQODUSA-N captafol Chemical compound C1C=CC[C@H]2C(=O)N(SC(Cl)(Cl)C(Cl)Cl)C(=O)[C@H]21 JHRWWRDRBPCWTF-OLQVQODUSA-N 0.000 claims description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims 2
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- WYDUFXRPFJPXGH-UHFFFAOYSA-N 7-methoxynaphthalene-1-carbaldehyde Chemical compound C1=CC=C(C=O)C2=CC(OC)=CC=C21 WYDUFXRPFJPXGH-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000004611 spectroscopical analysis Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- GABLTKRIYDNDIN-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1CCC(=O)C2=CC(OC)=CC=C21 GABLTKRIYDNDIN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- -1 -(Cfh^-Cfb Chemical group 0.000 description 2
- KVHHMYZBFBSVDI-UHFFFAOYSA-N 8-aminonaphthalen-2-ol Chemical compound C1=C(O)C=C2C(N)=CC=CC2=C1 KVHHMYZBFBSVDI-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 238000005899 aromatization reaction Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 150000004678 hydrides Chemical group 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000002790 naphthalenes Chemical class 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 230000006103 sulfonylation Effects 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- UFMVAMMCYVBZAS-UHFFFAOYSA-N (1-formyl-7-methoxynaphthalen-2-yl) methanesulfonate Chemical compound CS(=O)(=O)OC1=C(C2=CC(=CC=C2C=C1)OC)C=O UFMVAMMCYVBZAS-UHFFFAOYSA-N 0.000 description 1
- VDIFLYQCJAFOLQ-UHFFFAOYSA-N 2-(7-methoxynaphthalen-1-yl)ethanol Chemical compound C1=CC=C(CCO)C2=CC(OC)=CC=C21 VDIFLYQCJAFOLQ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
- 208000027559 Appetite disease Diseases 0.000 description 1
- ZWLRYJCLGKCHMF-UHFFFAOYSA-N COC1=CC=C2C=CC(=CC2=C1)O.OC1=C(C2=CC(=CC=C2C=C1)OC)C=O Chemical compound COC1=CC=C2C=CC(=CC2=C1)O.OC1=C(C2=CC(=CC=C2C=C1)OC)C=O ZWLRYJCLGKCHMF-UHFFFAOYSA-N 0.000 description 1
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 208000001456 Jet Lag Syndrome Diseases 0.000 description 1
- MPIMZAKRTOXRAO-UHFFFAOYSA-N N[C]N Chemical class N[C]N MPIMZAKRTOXRAO-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001343 alkyl silanes Chemical class 0.000 description 1
- TVJORGWKNPGCDW-UHFFFAOYSA-N aminoboron Chemical compound N[B] TVJORGWKNPGCDW-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- RJTANRZEWTUVMA-UHFFFAOYSA-N boron;n-methylmethanamine Chemical compound [B].CNC RJTANRZEWTUVMA-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007333 cyanation reaction Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- XYYQWMDBQFSCPB-UHFFFAOYSA-N dimethoxymethylsilane Chemical compound COC([SiH3])OC XYYQWMDBQFSCPB-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 230000001193 melatoninergic effect Effects 0.000 description 1
- 150000002815 nickel Chemical class 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000012672 seasonal affective disease Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/11—Aldehydes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/86—Use of additives, e.g. for stabilisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/575—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing ether groups, groups, groups, or groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (22)
1. Fremgangsmåde til industriel syntese af forbindelsen med formel (I):
O) kendetegnet ved, at 7-methoxy-naphthalen-2-ol med formel (III):
m omsættes, ved hvilken omsætning en formylgruppe indføres i position 1 for at give forbindelsen med formel (IV):
(TV) hvilken forbindelse med formel (IV) udsættes for en sulfonyleringsreaktion for at give forbindelsen med formel (V):
(V) hvor R betegner en gruppe -CH3, -(CH2)2-CH3, -CF3 eller toluyl; hvilken forbindelse med formel (V) undergår en deoxygeneringsreaktion i nærvær af et overgangsmetal og et reduktionsmiddel for at opnå forbindelsen med formel (I), som isoleres i form af et faststof.
2. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at R betegner en -CH3- eller toluyovergangsmetalletlgruppe.
3. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at omdannelsen af forbindelsen med formel (IV) til en forbindelse med formlen (V) udføres ved virkning af et sulfonylchlorid eller et sulfonsyreanhydrid eller et sulfonimid.
4. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 3, kendetegnet ved, at omdannelsen af forbindelsen med formel (IV) til en forbindelse med formlen (V) udføres ved virkning af et sulfonylchlorid.
5. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at det under omdannelse af forbindelsen med formel (V) til en forbindelse med formel (I) anvendte overgangsmetal er nikkel, palladium eller platin.
6. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at det under omdannelsen af forbindelsen med formel (V) til en forbindelse med formlen (I) anvendte overgangsmetal er et palladiumsalt.
7. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at omdannelsen af forbindelsen med formlen (V) til en forbindelse med formel (I) udføres i dimethylformamid, dioxan, tetrahydrofuran eller toluen.
8. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 7, kendetegnet ved, at omdannelsen af forbindelsen med formlen (V) til en forbindelse med formlen (I) udføres i dimethylformamid.
9. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at omdannelsen af forbindelsen med formlen (V) til en forbindelse med formlen (I) udføres mellem 25 °C og 110 °C.
10. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 9, kendetegnet ved, at omdannelsen af forbindelsen med formlen (V) til en forbindelse med formlen (I) udføres mellem 40 °C og 95 °C.
11. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at reduktionsmidlet under omdannelsen af forbindelsen med formlen (V) til en forbindelse med formlen (I) er dihydrogen.
12. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 11, kendetegnet ved, at dihydrogenet opnås ved dekomponering af et ammoniumformiat.
13. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at omdannelsen af forbindelsen med formel (V) til en forbindelse med formlen (I) udføres i nærvær af palladium og dihydrogen.
14. Fremgangsmåde til industriel syntese af forbindelsen med formel (I) ifølge krav 1, kendetegnet ved, at omdannelsen af forbindelsen med formlen (V) til en forbindelse med formel (I) udføres i nærvær af (9,9-dimethyl-9FI-xanthen)-4,5-diyl)-bis(diphenylphosphan) eller 1,3-bis(diphenylphosphino)-propan.
15. Forbindelse med formlen (V) ifølge krav 1 der er nyttig som et mellemprodukt ved syntesen af forbindelsen med formel (I).
16. Forbindelse med formel (V) ifølge krav 15 der er nyttig som et mellemprodukt ved syntesen af agomelatin med formel (II).
17. Forbindelse med formel (V) ifølge krav 15 og 16 der er valgt blandt følgende forbindelser: -1 -formyl-7-methoxynaphthalen-2-yl-4-methylbenzensulfonat; -1 -formyl-7-methoxynaphthalen-2-yl-methansulfonat.
18. Anvendelse af forbindelsen med formel (V) ifølge krav 15 til 17 ved syntesen af forbindelsen med formel (I).
19. Anvendelse af forbindelsen med formel (V) ifølge krav 18 ved syntesen af agomelatin med formel (II).
20. Anvendelse af forbindelsen med formel (III) ifølge krav 1 ved syntesen af forbindelsen med formel (I).
21. Anvendelse af forbindelsen med formel (III) ifølge krav 20 ved syntesen af agomelatin med formel (II).
22. Fremgangsmåde til syntesen af agomelatin fra forbindelsen med formel (V), kendetegnet ved, at forbindelsen med formel (V) opnås ved en syntesefremgangsmåde ifølge et af kravene 1 til 4.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1362200A FR3014434B1 (fr) | 2013-12-05 | 2013-12-05 | Nouveau procede de synthese du 7-methoxy-naphtalene-1-carbaldehyde et application a la synthese de l'agomelatine |
| PCT/FR2014/053159 WO2015082849A2 (fr) | 2013-12-05 | 2014-12-04 | Nouveau procede de synthese du 7-methoxy-naphtalene-1-carbaldehyde et application a la synthese de l'agomelatine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3077355T3 true DK3077355T3 (da) | 2018-05-22 |
Family
ID=50482960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK14821796.1T DK3077355T3 (da) | 2013-12-05 | 2014-12-04 | Ny fremgangsmåde til syntese af 7-methoxy-napthalen-1-carbaldehyd og anvendelse deraf i syntese af agomelatin |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US9701608B2 (da) |
| EP (1) | EP3077355B1 (da) |
| JP (1) | JP2016539169A (da) |
| KR (1) | KR20170018799A (da) |
| CN (1) | CN105793226B (da) |
| AU (1) | AU2014358967B2 (da) |
| CA (1) | CA2932196C (da) |
| CY (1) | CY1120160T1 (da) |
| DK (1) | DK3077355T3 (da) |
| EA (1) | EA031684B1 (da) |
| ES (1) | ES2668527T3 (da) |
| FR (1) | FR3014434B1 (da) |
| GE (1) | GEP20186847B (da) |
| HR (1) | HRP20180693T1 (da) |
| HU (1) | HUE036874T2 (da) |
| LT (1) | LT3077355T (da) |
| MA (1) | MA39062B1 (da) |
| MD (1) | MD20160072A2 (da) |
| ME (1) | ME03048B (da) |
| MX (1) | MX2016007130A (da) |
| NO (1) | NO3077355T3 (da) |
| PL (1) | PL3077355T3 (da) |
| PT (1) | PT3077355T (da) |
| RS (1) | RS56933B1 (da) |
| RU (1) | RU2680243C1 (da) |
| SI (1) | SI3077355T1 (da) |
| TR (1) | TR201802197T4 (da) |
| UA (1) | UA117940C2 (da) |
| WO (1) | WO2015082849A2 (da) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2658818B1 (fr) * | 1990-02-27 | 1993-12-31 | Adir Cie | Nouveaux derives a structure naphtalenique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| KR100849559B1 (ko) * | 2004-01-22 | 2008-07-31 | 일라이 릴리 앤드 캄파니 | 혈관운동 증상의 치료를 위한 선택적 에스트로겐 수용체조절제 |
| FR2866337B1 (fr) * | 2004-02-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese du (7-methoxy-1-naphtyl) acetonitrile et application a la synthese de l'aglomelatine |
| FR2866335B1 (fr) | 2004-02-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'agomelatine |
| FR2918369B1 (fr) * | 2007-07-02 | 2009-08-28 | Servier Lab | Nouveaux derives naphtaleniques,leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CN101638376B (zh) * | 2008-07-29 | 2011-04-27 | 江苏恩华药业股份有限公司 | 阿戈美拉汀的制备方法及其中间体 |
| FR2934859B1 (fr) * | 2008-08-05 | 2010-08-13 | Servier Lab | Nouveau procede de synthese de l'agomelatine |
-
2013
- 2013-12-05 FR FR1362200A patent/FR3014434B1/fr not_active Expired - Fee Related
-
2014
- 2014-04-12 UA UAA201606901A patent/UA117940C2/uk unknown
- 2014-12-04 SI SI201430642T patent/SI3077355T1/en unknown
- 2014-12-04 AU AU2014358967A patent/AU2014358967B2/en not_active Ceased
- 2014-12-04 CN CN201480066210.9A patent/CN105793226B/zh not_active Expired - Fee Related
- 2014-12-04 RU RU2016126660A patent/RU2680243C1/ru active
- 2014-12-04 GE GEAP201414198A patent/GEP20186847B/en unknown
- 2014-12-04 CA CA2932196A patent/CA2932196C/fr not_active Expired - Fee Related
- 2014-12-04 MD MDA20160072A patent/MD20160072A2/ro not_active Application Discontinuation
- 2014-12-04 JP JP2016536761A patent/JP2016539169A/ja not_active Ceased
- 2014-12-04 KR KR1020167017809A patent/KR20170018799A/ko not_active Application Discontinuation
- 2014-12-04 WO PCT/FR2014/053159 patent/WO2015082849A2/fr active Application Filing
- 2014-12-04 HU HUE14821796A patent/HUE036874T2/hu unknown
- 2014-12-04 ES ES14821796.1T patent/ES2668527T3/es active Active
- 2014-12-04 LT LTEP14821796.1T patent/LT3077355T/lt unknown
- 2014-12-04 EA EA201600439A patent/EA031684B1/ru not_active IP Right Cessation
- 2014-12-04 DK DK14821796.1T patent/DK3077355T3/da active
- 2014-12-04 MX MX2016007130A patent/MX2016007130A/es unknown
- 2014-12-04 US US15/101,120 patent/US9701608B2/en active Active
- 2014-12-04 ME MEP-2018-43A patent/ME03048B/me unknown
- 2014-12-04 TR TR2018/02197T patent/TR201802197T4/tr unknown
- 2014-12-04 RS RS20180247A patent/RS56933B1/sr unknown
- 2014-12-04 PL PL14821796T patent/PL3077355T3/pl unknown
- 2014-12-04 EP EP14821796.1A patent/EP3077355B1/fr active Active
- 2014-12-04 PT PT148217961T patent/PT3077355T/pt unknown
- 2014-12-04 MA MA39062A patent/MA39062B1/fr unknown
- 2014-12-04 NO NO14821796A patent/NO3077355T3/no unknown
-
2018
- 2018-05-02 CY CY20181100451T patent/CY1120160T1/el unknown
- 2018-05-03 HR HRP20180693TT patent/HRP20180693T1/hr unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101127278B1 (ko) | 아고멜라틴의 합성 방법 | |
| KR101135336B1 (ko) | 아고멜라틴의 합성 방법 | |
| BG64986B1 (bg) | Метод за получаването на 5-цианфталид | |
| JPWO2014042176A1 (ja) | 縮合複素環誘導体の製造方法およびその製造中間体 | |
| RU2683279C1 (ru) | Новый способ синтеза агомелатина | |
| CN111943901A (zh) | 一种由炔酰胺直接合成噁唑烷-2，4-二酮类杂环化合物的方法 | |
| DK3077355T3 (da) | Ny fremgangsmåde til syntese af 7-methoxy-napthalen-1-carbaldehyd og anvendelse deraf i syntese af agomelatin | |
| Cheng et al. | Synthetic approaches to 2‐substituted 1‐oxo‐and 3‐oxotetrahydroisoquinolines | |
| JP5837616B2 (ja) | アゴメラチン合成のための方法及び中間体 | |
| TWI844663B (zh) | 製造經取代之2-[2-(苯基)乙胺]烷醯胺衍生物之方法 | |
| TWI500596B (zh) | 合成３，４－二甲氧基雙環［４．２．０］辛－１，３，５－三烯－７－甲腈之方法，及於合成依伐布雷定（ｉｖａｂｒａｄｉｎｅ）及其與醫藥上可接受酸之加成鹽之應用 | |
| BRPI0618641A2 (pt) | compostos orgánicos | |
| WO2014087105A1 (fr) | Nouveau procede de synthese du 3-(2-bromo-4,5-dimethoxyphenyl)propanenitrile, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable | |
| KR101695346B1 (ko) | 이보두탄트（ｍｅｎ15596）및 관련 중간체의 제조 방법 | |
| WO2015082848A2 (fr) | Nouveau procede de synthese du 7-methoxy-naphtalene-1-carbaldehyde et application a la synthese de l'agomelatine | |
| KR20070057693A (ko) | 에네-아마이드 유도체의 제조 방법 | |
| JP2014196299A (ja) | ７，８−ジメトキシ−１，３−ジヒドロ−２ｈ−３−ベンゾアゼピン−２−オン化合物の合成方法及びイバブラジンの合成における適用 | |
| ITMI962363A1 (it) | Procedimento migliorato per la preparazione di 1,1-dimetil-2-(n- metil-n-(3,3-difenil propil)amminoetanolo |