WO2018168815A1 - ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法 - Google Patents

３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法 Download PDF

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Publication number
WO2018168815A1
WO2018168815A1 PCT/JP2018/009596 JP2018009596W WO2018168815A1 WO 2018168815 A1 WO2018168815 A1 WO 2018168815A1 JP 2018009596 W JP2018009596 W JP 2018009596W WO 2018168815 A1 WO2018168815 A1 WO 2018168815A1
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Prior art keywords
formula
added
compound
salt
pyridazine
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PCT/JP2018/009596
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English (en)
French (fr)
Japanese (ja)
Inventor
亮史 小池
芳文 蓮
隆文 北脇
昇平 白石
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Daiichi Sankyo Co Ltd
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Daiichi Sankyo Co Ltd
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Priority to CA3055504A priority Critical patent/CA3055504A1/en
Priority to EP22186787.2A priority patent/EP4101853A1/en
Priority to PL18766623.5T priority patent/PL3597648T3/pl
Priority to RS20230550A priority patent/RS64354B1/sr
Priority to JP2019506027A priority patent/JP7082608B2/ja
Priority to ES18766623T priority patent/ES2947326T3/es
Priority to SM20230269T priority patent/SMT202300269T1/it
Priority to HRP20230764TT priority patent/HRP20230764T1/hr
Priority to US16/494,116 priority patent/US11028091B2/en
Priority to CN202210636460.8A priority patent/CN114773351A/zh
Priority to CN201880017847.7A priority patent/CN110418792B/zh
Application filed by Daiichi Sankyo Co Ltd filed Critical Daiichi Sankyo Co Ltd
Priority to EP18766623.5A priority patent/EP3597648B1/en
Priority to AU2018234027A priority patent/AU2018234027B2/en
Publication of WO2018168815A1 publication Critical patent/WO2018168815A1/ja
Anticipated expiration legal-status Critical
Priority to US17/164,684 priority patent/US11667642B2/en
Priority to JP2022086917A priority patent/JP7384963B2/ja
Priority to US18/183,039 priority patent/US20230227459A1/en
Priority to JP2023143544A priority patent/JP2023171735A/ja
Priority to JP2025106052A priority patent/JP2025123513A/ja
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/02—Dicarboxylic acids
    • C07C55/14—Adipic acid
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods
    • 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

Definitions

  • the present invention relates to a novel method for producing a 3,6-disubstituted imidazo [1,2-b] pyridazine derivative.
  • 3,6-disubstituted imidazo [1,2-b] pyridazine derivatives are known to be useful as pharmaceuticals or raw materials for producing them and to be useful in the treatment of tumors (Patent Document 1).
  • Patent Document 1 all 3,6-disubstituted imidazo [1,2-b] pyridazine derivatives are aromatic nucleophilic compounds starting from 3-bromo-6-chloroimidazo [1,2-b] pyridazine. It is synthesized by introducing a substituent at the 6-position using a substitution reaction and then introducing the substituent at the 3-position using a Suzuki-Miyaura coupling reaction (Patent Document 1, for example, Example 21).
  • Non-patent Document 1 As another synthesis method of 3,6-disubstituted imidazo [1,2-b] pyridazine derivatives, starting from 6-chloroimidazo [1,2-b] pyridazine, palladium is added at the 3-position of the compound. A method of introducing an aryl group using an aromatic substitution reaction utilizing C—H activation by is known (Non-patent Document 1).
  • Patent Document 1 has a restriction that a halogen atom is essential at the reaction point of the Suzuki-Miyaura coupling reaction on the imidazo [1,2-b] pyridazine ring.
  • the present invention relates to 3,6-disubstituted imidazo [1,2 using an aromatic substitution reaction using CH activation with palladium starting from 6-fluoroimidazo [1,2-b] pyridazine.
  • -B A method for producing a pyridazine derivative, wherein the amount of palladium catalyst used is small, and an aryl group having an electron-donating substituent having a complicated structure can be introduced in high yield. It provides a useful and novel method.
  • the present invention relates to the following (1) to (7).
  • a method comprising producing a compound represented by the formula (V) using the production method described in (6) and then chlorinating using adipic acid, The manufacturing method of the adipate of the compound represented by these.
  • palladium catalyst means a divalent palladium catalyst or a zero-valent palladium catalyst.
  • An example is tris (2-methylphenyl) phosphine palladium (0).
  • the “palladium catalyst” of the present invention includes, for example, palladium compounds such as palladium chloride and palladium acetate, and monodentate phosphines such as triphenylphosphine, tri-t-butylphosphine, tris (2-methylphenyl) phosphine, etc.
  • phosphine ligand such as 1,1-bis (diphenylphosphino) methane, 1,2-bis (diphenylphosphino) ethane Catalyst.
  • the reaction can be carried out using a very small amount of palladium catalyst.
  • the amount of palladium catalyst used is preferably 0.5 to 10 mol%, more preferably 1 to 5 mol%, relative to the compound of formula (I). More preferably, it is 2 mol%.
  • the nitrogen atom protecting group (PG) that can be used in the present invention may be any substituent that reduces the reactivity of the nitrogen atom to the electrophilic addition reaction.
  • PG nitrogen atom protecting group
  • TW Protective Groups in Organic Synthesis
  • PMGM Green and PMGM Wuts, John Wiley & Sons, Inc., New York, 1991
  • Preferred are a tert-butoxycarbonyl group and a benzyloxycarbonyl group.
  • the solvent that can be used in the present invention is not particularly limited as long as it does not inhibit the aromatic substitution reaction using the C—H activation reaction with palladium.
  • Examples thereof include toluene, cyclopentyl methyl ether, 1,4-dioxane, diethylene glycol dimethyl ether and the like.
  • a solvent miscible with water is preferred, and examples thereof include diethylene glycol dimethyl ether.
  • the compound represented by the formula (III) and the compound represented by the formula (V) of the present invention can be converted into a salt by reacting with an acid.
  • hydrohalides such as hydrofluoride, hydrochloride, hydrobromide, hydroiodide, inorganic acid salts such as nitrate, perchlorate, sulfate, phosphate; methane C 1 -C 6 alkyl sulfonates such as sulfonate, trifluoromethane sulfonate, ethane sulfonate, aryl sulfonate such as benzene sulfonate, p-toluene sulfonate, acetate, Organic acid salts such as malate, fumarate, succinate, citrate, ascorbate, tartrate, succinate, adipate; and glycine, lysine, arginine, ornithine And amino acid salts such as glutamate and aspartate.
  • inorganic acid salts such as nitrate, perchlorate, sulfate, phosphate
  • the compound represented by the formula (III) or a salt thereof, the compound represented by the formula (V) or a salt thereof of the present invention is left in the atmosphere or recrystallized to form a water molecule. May be formed into a hydrate, and such a hydrate is also included in the present invention.
  • the compound of the present invention represented by the formula (III) or a salt thereof, and the compound represented by the formula (V) or a salt thereof are allowed to stand in a solvent or recrystallize to give a certain kind.
  • the solvent may be absorbed to form a solvate, and such a solvate is also encompassed in the present invention.
  • the present invention relates to 3,6-disubstituted imidazo [1,2 using an aromatic substitution reaction using CH activation with palladium starting from 6-fluoroimidazo [1,2-b] pyridazine.
  • -B A method for producing a pyridazine derivative, wherein the amount of palladium catalyst used is small, and an aryl group having an electron-donating substituent having a complicated structure can be introduced in high yield.
  • a useful and novel method can be provided.
  • the reaction conditions of the present invention should not be construed as being limited thereto.
  • the functional group of the compound may be protected with an appropriate protecting group.
  • Examples of such functional groups include a hydroxyl group, a carboxy group, an amino group, and the like.
  • the types of protecting groups and the conditions for introducing and removing these protecting groups are, for example, Protective Groups in Organic Synthesis (T. W. Green and PMGM Wuts, John Wiley & Sons, Inc., New York, 1991) can be referred to.
  • crystallization of the compound (6) obtained in Example 7 is shown.
  • the vertical axis in the figure indicates the diffraction intensity as a relative linear intensity (count), and the horizontal axis indicates the value of the diffraction angle 2 ⁇ .
  • nuclear magnetic resonance (hereinafter, 1 H NMR: 400 MHz) spectra are described with chemical shift values as ⁇ values (ppm) using tetramethylsilane as a standard substance.
  • the splitting pattern is indicated by s for single lines, d for double lines, dd for double double lines, m for multiple lines, and br for broad lines.
  • the aqueous layer was extracted twice with isopropyl acetate (500 mL), and all the organic layers were combined.
  • the combined organic layers were washed twice with water (500 mL), and the resulting organic layer was concentrated under reduced pressure to 300 mL.
  • the operation of adding ethanol (1000 mL) and concentrating under reduced pressure to 300 mL was repeated twice.
  • tetrahydrofuran 200 mL was added and cooled to 5 ° C or lower.
  • Di-tert-butyl dicarbonate (162 g, 0.74 mol, 1.3 equiv.) was dissolved in tetrahydrofuran (100 mL) and added dropwise at about 6 ° C or less over about 2 hours. After stirring at 5 ° C or lower for 1 hour, the temperature was raised to about 20 ° C and stirred overnight. After adding ethanol (230 mL), water (800 mL) was added dropwise over 1.5 hours. After stirring at about 50 ° C for 1 hour or longer, the mixture was gradually cooled to 25 ° C and stirred overnight. The precipitated solid was filtered and washed with a mixed solution of ethanol (230 mL) and water (270 mL). Vacuum drying at an external temperature of 40 ° C. gave the title compound (1) (170 g).
  • dimethyl sulfoxide (1500 mL), benzyltriethylammonium chloride (445 g, 1.95 mol, 1 equiv.), 6-chloroimidazo [1,2-b] pyridazine (300 g, 1.95 mol, 1 equiv) .) (Available for purchase from Combi-Block, etc.).
  • cesium fluoride (534 g, 3.51 mol, 1.8 equiv.) was added, and the mixture was stirred at an internal temperature of 79 to 81 C for 4 hours.
  • dimethyl sulfoxide (2.4 L) was added to (1R) -1- (3-fluorophenyl) ethanamine (400 g, 2.87 mol, 1 equiv.), Trisodium phosphate (471 g, 2.87 mol, 1 equiv. ) And the compound of formula (3) (1.22 kg (net weight 1.12 kg), 3.16 mol, 1.1 equiv) were sequentially added. This mixture was heated and stirred at an internal temperature of 95 to 99 ° C. for 55 hours. After cooling, cyclopentyl methyl ether (4 L) and water (8 L) were added at an internal temperature of 24 ° C. After heating to 50 ° C.
  • the compound of formula (4) (120.0 g) was dissolved in ethanol (1080 g), and activated carbon (12 g) wetted with ethanol (60 g) was added. After stirring for 1 hour, the mixture was filtered and washed with ethanol (120 mL). Concentrated hydrochloric acid (43.3 g) was added to the resulting solution, and the mixture was heated and stirred at 65 to 70 ° C. for 4 hours. The mixture was cooled to an internal temperature of 20 ° C. over 2 hours, stirred at that temperature for 1 hour, and further cooled to 1 ° C. over 1 hour. After stirring at an internal temperature of ⁇ 1 to 1 ° C. for 19.5 hours, the precipitated solid was filtered and washed with a cooled mixed solution of ethanol (240 mL) and water (6 mL). It was dried at 40 ° C. under reduced pressure to obtain the title compound (5) (100.5 g).
  • Non-Patent Document 1 palladium acetate 0.1 equiv., Triphenylphosphine 0.2 equiv., Potassium carbonate 2 equiv.
  • the reaction rate of the compound of formula (7) was about 1.4% on HPLC.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Catalysts (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Plural Heterocyclic Compounds (AREA)
PCT/JP2018/009596 2017-03-14 2018-03-13 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法 Ceased WO2018168815A1 (ja)

Priority Applications (18)

Application Number Priority Date Filing Date Title
CN201880017847.7A CN110418792B (zh) 2017-03-14 2018-03-13 制备3,6-二取代咪唑并[1,2-b]哒嗪衍生物的方法
PL18766623.5T PL3597648T3 (pl) 2017-03-14 2018-03-13 METODA WYTWARZANIA 3,6-DIPODSTAWIONEJ POCHODNEJ IMIDAZO[1, 2-b]PIRYDAZYNY
RS20230550A RS64354B1 (sr) 2017-03-14 2018-03-13 Postupak za proizvodnju derivata 3, 6-disupstituisanog imidazo[1, 2-b]piridazina
JP2019506027A JP7082608B2 (ja) 2017-03-14 2018-03-13 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法
ES18766623T ES2947326T3 (es) 2017-03-14 2018-03-13 Procedimiento de producción de un derivado de imidazo[1,2-b]piridazina 3,6-disubstituido
SM20230269T SMT202300269T1 (it) 2017-03-14 2018-03-13 Metodo per produrre un imidazo[1,2-b]piridazina-derivato 3,6-disostituito
HRP20230764TT HRP20230764T1 (hr) 2017-03-14 2018-03-13 POSTUPAK ZA PROIZVODNJU DERIVATA 3, 6-DISUPSTITUIRANOG IMIDAZOL[1, 2-b]PIRIDAZINA
US16/494,116 US11028091B2 (en) 2017-03-14 2018-03-13 Method for producing 3, 6-disubstituted imidazo[1, 2-b]pyridazine derivative
EP18766623.5A EP3597648B1 (en) 2017-03-14 2018-03-13 METHOD FOR PRODUCING 3, 6-DISUBSTITUTED IMIDAZO[1, 2-b]PYRIDAZINE DERIVATIVE
CA3055504A CA3055504A1 (en) 2017-03-14 2018-03-13 Method for producing 3,6-disubstituted imidazo[1,2-b]pyridazine derivative
EP22186787.2A EP4101853A1 (en) 2017-03-14 2018-03-13 Method for producing 3,6-disubstituted-imidazo[1,2-b]pyridazine derivative
CN202210636460.8A CN114773351A (zh) 2017-03-14 2018-03-13 制备3,6-二取代咪唑并[1,2-b]哒嗪衍生物的方法
AU2018234027A AU2018234027B2 (en) 2017-03-14 2018-03-13 Method for producing 3, 6-disubstituted imidazo[1, 2-b]pyridazine derivative
US17/164,684 US11667642B2 (en) 2017-03-14 2021-02-01 Method for producing 3,6-disubstituted-imidazo[1,2-b]pyridazine derivative
JP2022086917A JP7384963B2 (ja) 2017-03-14 2022-05-27 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法
US18/183,039 US20230227459A1 (en) 2017-03-14 2023-03-13 Method for producing 3,6-disubstituted-imidazo[1,2-b]pyridazine derivative
JP2023143544A JP2023171735A (ja) 2017-03-14 2023-09-05 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法
JP2025106052A JP2025123513A (ja) 2017-03-14 2025-06-24 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法

Applications Claiming Priority (2)

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JP2017-049138 2017-03-14
JP2017049138 2017-03-14

Related Child Applications (2)

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US16/494,116 A-371-Of-International US11028091B2 (en) 2017-03-14 2018-03-13 Method for producing 3, 6-disubstituted imidazo[1, 2-b]pyridazine derivative
US17/164,684 Division US11667642B2 (en) 2017-03-14 2021-02-01 Method for producing 3,6-disubstituted-imidazo[1,2-b]pyridazine derivative

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US (3) US11028091B2 (https=)
EP (2) EP3597648B1 (https=)
JP (4) JP7082608B2 (https=)
CN (2) CN110418792B (https=)
AU (1) AU2018234027B2 (https=)
CA (1) CA3055504A1 (https=)
ES (1) ES2947326T3 (https=)
HR (1) HRP20230764T1 (https=)
HU (1) HUE063830T2 (https=)
PL (1) PL3597648T3 (https=)
RS (1) RS64354B1 (https=)
SM (1) SMT202300269T1 (https=)
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2022105746A (ja) * 2017-03-14 2022-07-14 第一三共株式会社 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法
WO2023220967A1 (en) * 2022-05-18 2023-11-23 Anheart Therapeutics (Hangzhou) Co., Ltd. Method for producing 3,6-disubstituted-imidazo[1,2-b]pyridazine compounds
JP2024525230A (ja) * 2021-07-01 2024-07-10 アンハート セラピューティクス（ハンチョウ）コーポレーション，リミテッド ３－｛４－［（２ｒ）－２－アミノプロポキシ］フェニル｝－ｎ－［（１ｒ）－１－（３－フルオロフェニル）エチル］イミダゾ［１，２－ｂ］ピリダジン－６－アミンおよびその塩の結晶形態

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60197640A (ja) * 1984-03-19 1985-10-07 Ihara Chem Ind Co Ltd ハロゲン化ニトロベンゼン類の製造方法
JPS61205220A (ja) * 1985-03-08 1986-09-11 Rikagaku Kenkyusho 一級アルコ−ル類の選択的フツ素化方法
JPH08119970A (ja) * 1994-10-21 1996-05-14 Mitsubishi Chem Corp 新規ビスオキサゾリン化合物
JP2002193914A (ja) * 2000-05-24 2002-07-10 Nissan Chem Ind Ltd ニトリル化合物およびその製造方法
JP2010531342A (ja) * 2007-06-28 2010-09-24 サノフイ−アベンテイス ６−シクロアミノ−３−（ピリジン−４−イル）イミダゾ［１，２−ｂ］ピリダジン誘導体、これらの調製およびこれらの治療的使用
JP2011530574A (ja) * 2008-08-12 2011-12-22 サノフイ−アベンテイス ２−アルキル−６−シクロアミノ−３−（ピリジン−４−イル）イミダゾ［１，２−ｉｂ］ピリダジン誘導体、この調製およびこの治療応用
WO2013183578A1 (ja) 2012-06-04 2013-12-12 第一三共株式会社 キナーゼ阻害剤としてのイミダゾ[１，２－ｂ]ピリダジン誘導体
US20140364413A1 (en) * 2013-06-11 2014-12-11 Janssen Pharmaceutica, Nv PDE 10a Inhibitors for the Treatment of Type II Diabetes
JP2015509534A (ja) * 2012-03-09 2015-03-30 レクシコン ファーマシューティカルズ インコーポレイテッド イミダゾ［１，２−ｂ］ピリダジン系化合物、それを含む組成物、及びそれらを使用する方法
JP2016510764A (ja) * 2013-03-07 2016-04-11 カリフィア バイオ, インク.Califia Bio, Inc. 混合系キナーゼ阻害剤および治療法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2001260607A1 (en) * 2000-05-24 2001-12-03 Nissan Chemical Industries Ltd. Nitrile compounds and process for their preparation
HUE063830T2 (hu) 2017-03-14 2024-02-28 Daiichi Sankyo Co Ltd Eljárás 3,6-diszubsztituált imidazo[1,2-b]piridazin származék elõállításához
JP7648372B2 (ja) * 2020-11-30 2025-03-18 株式会社ファンケル クロロフィル含有食品用緑色退色抑制剤

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60197640A (ja) * 1984-03-19 1985-10-07 Ihara Chem Ind Co Ltd ハロゲン化ニトロベンゼン類の製造方法
JPS61205220A (ja) * 1985-03-08 1986-09-11 Rikagaku Kenkyusho 一級アルコ−ル類の選択的フツ素化方法
JPH08119970A (ja) * 1994-10-21 1996-05-14 Mitsubishi Chem Corp 新規ビスオキサゾリン化合物
JP2002193914A (ja) * 2000-05-24 2002-07-10 Nissan Chem Ind Ltd ニトリル化合物およびその製造方法
JP2010531342A (ja) * 2007-06-28 2010-09-24 サノフイ−アベンテイス ６−シクロアミノ−３−（ピリジン−４−イル）イミダゾ［１，２−ｂ］ピリダジン誘導体、これらの調製およびこれらの治療的使用
JP2011530574A (ja) * 2008-08-12 2011-12-22 サノフイ−アベンテイス ２−アルキル−６−シクロアミノ−３−（ピリジン−４−イル）イミダゾ［１，２−ｉｂ］ピリダジン誘導体、この調製およびこの治療応用
JP2015509534A (ja) * 2012-03-09 2015-03-30 レクシコン ファーマシューティカルズ インコーポレイテッド イミダゾ［１，２−ｂ］ピリダジン系化合物、それを含む組成物、及びそれらを使用する方法
WO2013183578A1 (ja) 2012-06-04 2013-12-12 第一三共株式会社 キナーゼ阻害剤としてのイミダゾ[１，２－ｂ]ピリダジン誘導体
JP2016510764A (ja) * 2013-03-07 2016-04-11 カリフィア バイオ, インク.Califia Bio, Inc. 混合系キナーゼ阻害剤および治療法
US20140364413A1 (en) * 2013-06-11 2014-12-11 Janssen Pharmaceutica, Nv PDE 10a Inhibitors for the Treatment of Type II Diabetes

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BENDJEDDOU, Z. LYAMIN ET AL.: "Exploration of the imidazo[1,2-b]pyridazine scaffold as a protein kinase inhibitor", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 125, 22 September 2016 (2016-09-22), pages 696 - 709, XP029842425, ISSN: 0223-5234, DOI: doi:10.1016/j.ejmech.2016.09.064 *
EL, AKKAOUI, AHMED ET AL.: "Direct Arylation of Imidazo[1,2- b ]pyridazines: Microwave-Assisted One-Pot Suzuki Coupling/Pd-Catalysed Arylation", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 5, 2010, pages 862 - 871, XP055150274, ISSN: 1434-193X *
EUR. J. ORG. CHEM., 2010, pages 862 - 871
T. W. GREENP. G. M. WUTS: "Protective Groups in Organic Synthesis", 1991, JOHN WILEY & SONS, INC.

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2022105746A (ja) * 2017-03-14 2022-07-14 第一三共株式会社 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法
US11667642B2 (en) 2017-03-14 2023-06-06 Daiichi Sankyo Company, Limited Method for producing 3,6-disubstituted-imidazo[1,2-b]pyridazine derivative
JP7384963B2 (ja) 2017-03-14 2023-11-21 第一三共株式会社 ３，６－ジ置換イミダゾ［１，２－ｂ］ピリダジン誘導体の製造方法
JP2024525230A (ja) * 2021-07-01 2024-07-10 アンハート セラピューティクス（ハンチョウ）コーポレーション，リミテッド ３－｛４－［（２ｒ）－２－アミノプロポキシ］フェニル｝－ｎ－［（１ｒ）－１－（３－フルオロフェニル）エチル］イミダゾ［１，２－ｂ］ピリダジン－６－アミンおよびその塩の結晶形態
WO2023220967A1 (en) * 2022-05-18 2023-11-23 Anheart Therapeutics (Hangzhou) Co., Ltd. Method for producing 3,6-disubstituted-imidazo[1,2-b]pyridazine compounds

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